Index [pharmrev.aspetjournals.org] · 2005. 7. 26. · -dependent protein kinases, 306,308...
Transcript of Index [pharmrev.aspetjournals.org] · 2005. 7. 26. · -dependent protein kinases, 306,308...
605
0031-6997/4/4304-0605$02.00/0PHARMACOLOGICAL REVIEWS
Copyright © 1991 by The American Society for Pharmacology and Experimental Therapeutics
Index
Vol. 43, No.4Printed in U.S.A.
Pharmacological Reviews
Volume 43
1991
Acetyicholine, mechanism of action of antipsychotics, 588
Action potential, extracellular, NRM 5-HT neuron (fig.), 564Adenocarcinoma, mammary, nitric oxide synthase, 130
Adenosine
agonists and antagonists, cerebellar cGMP (table), 11
modulators, 6receptors for inhibitory agonists, 275
uptake and metabolism, 279
Adenosine 5’-diphosphate
extracellular, metabolism, 255
receptors for stimulatory agonista, 250
Adenylate cyclase
activation, ventricular G proteins, myopathy (table), 218
activation in end-stage 1CM, ventricular G proteins (table), 221
a,-a�noceptor-mediated inhibition (fig.), 492
coupling, beta adrenoceptors, 207
Adenylyl cyclase, inhibition, 486
Adrenal gland, cyclic GMP levels, 124
Adrenaline
-induced positive inotropic effects, left papillary muscles (fig.), 211
-induced stimulation of left ventricular adenylate cyclase, antago-
nism, beta adrenoceptors (fig.), 208
Adrenoceptors
agonists and antagonists (table), 477
alpha
guanine nucleotide regulatory proteins, 490
molecular biology, 500
occupancy and function, 488
proposed interaction (fig.), 493
signal transduction, 500signal transduction mechanisms, 483
structure and function, 475
subclassification, 499
alpha-i
cloning of DNAS, 493competition by agonista and antagonists (table), 495
functional expression, cDNAs, 495
heterogeneity, 477
alpha-2
alignment of amino acid sequences (fig.), 496
cloning of DNAs, 496
DNA expression, 498heterogeneity, 480
occupancy, signal transduction mechanisms, 489
primary structure, kidney (fig.), 497
signal transduction processes, mathematical model (fig.), 491
sodium-hydrogen exchange (fig.), 488
alpha-i and a�pha-2 classification, 476
betaagonists, maximal positive inotropic effects (fig.), 220
agonists, spare receptors in heart, 224
alterations, chronic heart failure, 223
antagonism, stimulation ofleft ventricular adenylate cyclase (fig.),
208
antagonist radioligands (table), 205
antagonists, 228
antagonists, right atria (fig.), 229
density, left ventricle (fig.), 225
effects of drugs, human heart, 228
failing human heart, 216
heart failure (fig.), 217
human heart, 203
left ventricular membranes (fig.), 205
maximal positive inotropic effect, right ventricular trabeculae
(fig.), 227
6 months treatment, metoprolol (fig.), 230
myocardial, subtype distribution (table), 222
nonfailing human heart, 205
positive inotropic drugs, 213
procaterol and noradrenaline (fig.), 229protein phosphorylation, 321
subtype distribution, heart failure (table), 218
subtype distribution, nonfailing human heart (table), 206
transplanted human heart, 226
Afferents, noradrenergic, 13
Ahlner, Johan, Rolf G. G. Andersson, Kristina Torfg#{226}rd, and Krister
L. Axelsson. Organic nitrate esters: Clinical use and mechanisms
of actions, 351
Airway diseases, nitrates, 391
Alcoholism, synapsin variants, 329
Alprazolam, stress and, corticotropin-releasing factor concentrations
(fig.), 455
Alzheimer’s disease
alterations, regional brain corticotropin-releasing factor concentra-
tions and receptors, 460
CRF-like immunoreactivity, receptor binding (fig.), 460
protein phosphorylation, 331
serotonin, 519
studies of m-chlorophenylpiperazine, 532
Amantadine, changes in motor activity, cerebellar cGMP (table), 3
Amino acids
alignment of sequences, alpha-2 adrenoceptors (fig.), 496
branched-chain, 56
branched-chain and aromatic, “false” neurotransmitters, 37
excitatory
GABAergic pathways and, 4
nonselective antagonists, 14
release, 13
-y-Aminobutyric acid
-benzodiazepine receptor complex, 42
-BzR/chloride ionophore supramolecular complex (fig.), 42
excitatory amino acids and, 4
mechanism of action of antipsychotics, 588
receptor complex organization, 41
-y-Aminobutyric acid-A, benzodiazepine receptor modulators, 5
-y-Aminobutyric acid-B, receptor agonista, 6
Ammonia, major contributor, hepatic encephalopathy, 35
Amperozide
pED,o (table), 594
pK1 values (table), 592
606 INDEX
D-Amphetamine, changes in motor activity, cerebellar cGMP (table),
3
fi-Amyloid, precursor protein phosphorylation, neuritic plaques, 333
Analgesia, brain 5-HT, 567
Andersson, Rolf G. G. See Ahlner et al., 351
Anesthetics, barbiturates and, cGMP in the cerebellum, 12
Angina
stable, organic nitrates, 382
unstable, silent myocardial ischemia, myocardial infarction, 387
vasospastic
glyceryl trinitrate, 386isosorbide dinitrate and isosorbide-5-mononitrate, 386
Angiotensin-converting enzyme inhibitors, beta adrenoceptors, 231
Anorexia nervosa, endocrine and cerebrospinal fluid studies, 460
Antibiotics, hepatic encephalopathy, 55
Anticonvulsants, cerebellar cGMP (table), 10
Antidiuretic hormone, disorders (table), 98
Antiemesis, 5-HT3 receptor agents, 582
Antipsychotics
atypical, 588
pED�o (table), 594
pK1 values, 5-HT2 (table), 592
serotonin receptor antagonism, 598
binding properties, serotonin receptors, 592
clinical studies, 599
cortical 5-HT, and striatal pK values (table), 593
effects on serotonin receptors, 587
mechanism of action, neurotransmitters, 588pKd or pK1 values, 5-HT receptors (table), 592
serotonin class 3 receptor antagonism, 598
serotonin-mediated behavior, 597
Anxiety
animal models, 449, 544
depression and, animal models, 537
Anxiety disorder
serotonin function, 516
studies of azapirones, 542
Aorta
effect of dexamethasone, constitutive and inducible nitric oxide
synthase (fig.), 132
time-dependent loss of tone, effect of cycloheximide, L-NIO (fig.),
130
Apomorphine, changes in motor activity, cerebellar cGMP (table), 3
Arachidonic acid, metabolites, vascular actions, organic nitrate esters,
366
L-Arginine
citrulline synthesis, Ca’ dependence, nitric oxide (fig.), 123
platelet aggregation, nitric oxide synthesis (fig.), 121
structural formulae (fig.), 116
Arginine vasopressin
elevated plasma levels, V, antagonists, 96
ethanol-induced gastric lesions (fig.), 87
Arylpiperazines, serotonin-selective, effects in humans, 527
Aspirin, indomethacin and, drug interactions, nitrates, 406
Atenololhuman cardiac beta adrenoceptors (fig.), 213
propranolol and, tachycardia (fig.), 212
Atropine, human cardiac beta adrenoceptors (fig.), 213
Aulakh, C. S. See Murphy et al., 527
Axelsson, Krister L. See Ahlner et a!., 351
Azapironesfood intake, 544
healthy normal subjects, 541
5-HT1A receptors, 541
in vitro and in animals, 543
locomotor activity, 544
neurochemical effects, 543
neuroendocrine measures, 544
patients with neuropsychiatric disorders, 542
Barbiturates, anesthetics and, cGMP in the cerebellum, 12
Basile, Anthony S., E. Anthony Jones, and Phil Skolnick. The patho-
genesis and treatment of hepatic eciphalopathy: Evidence for
the involvement of benzodiazepine receptor ligands, 27
Behavior
anxiety and depression, animal models, 449
corticotropin-releasing factor regulation, laboratory animals, 448
feeding, corticotropin-releasing factor, 449locomoter activation, corticotropin-releasing factor, 448
oral-buccal movements, 573serotonin-mediated, antipsychotic drugs, 597
serotonin-selective arylpiperazines, 527
sexual, corticotropin-releasing factor, 448Benzodiazepine
uganda (fig.), 43nuclei biosynthesis (fig.), 52
Bioassay, vasopressin antagonists, 75
Blood pressure
changes induced by oral administration, L-NAME and L-NMMA
(fig.), 117
DRN 5-HT neuron (fig.), 574
regulation, V1 antagonists, 78
Blood vessels, relaxant effect of glyceryl trinitrate (table), 355
BMY 25801, BRL 24924 and, clinical status (table), 583
Brain
cerebral aqueduct or locus ceruleus, corticotropin-releasing factor
infusion (fig.), 450developmental pharmacology, serotonin, other neurotransmitter, 553
energy metabolism, m-chlorophenylpiperazine, 538
first messengers regulating second messenger generation (table), 303
hypothalamic corticotropin-releasing factor neurons, actions of Cy-
tokines, 444
insulin-induced hypoglycemia, corticotropin-releasing factor mRNA
(fig.), 441
localization, corticotropin-releasmg factor receptors, 433
major corticotropin-releasing factor-stained cell groups, fiber systems
(fig.), 429
nigrostriatal and mesolimbic pathway, serotonergiC innervation, 590
nigrostriatal pathways, serotonergic regulation, dopaminergic func-
tion, 595
pED�, typical atypical antipsychotic drugs (table), 594
phosphoprotein phosphatases, 312
prevention of hyponatremia and cerebral edema, V, antagonists, 88
serine/threonine-specific protein phosphatases (table), 312
serotonergic neurons, behaving animal, 563
specific regions, topical administration, capsaicin, 164water content, serum osmolality, vasopressin antagonist (table), 90
Brodde, Otto-Erich. �- and �9,-adrenoceptors in the human heart:
Properties, function, and alterations in chronic heart failure,
203
Bulimia, migraine and, 532
Buspirone
neuroendocrine responses, 514
single-dose studies in humans, 541
Calcium
antagonists, 230
dependence of nitric oxide and citrulline synthesis, L-arginine, brain
synaptosomal cytosol (fig.), 123
-dependent protein kinases, 306, 308
homeostasis, organic nitrate esters, cyclic GMP, 363-independent nitric oxide synthase (fig.), 129
influx, phosphorylation of GAP-43, 318peak positive left ventricular dP/dT (fig.), 223
-phospholipid-dependent protein kinases, 309
INDEX 607
signal transduction, second messenger systems, 433
sodium chloride and, intracellular accumulation, neurotoxicity, 181
translocation, alpha adrenoceptor signal transduction, 483
Calcium channels, voltage-dependent, 324
Calcium current, capsaicin administration, 176
Capsaicinaction
excitable cells (table), 188neurons, 189
primary afferent neurons, 145
acute and long-term effects, nonmammalian species, 168acute excitatory effects, mammalian sensory neurons, 146
administered to central endings, afferent neurons, 163
administered to peripheral endings, sensory neurons, 164biochemical characterization, recognition site, 174
cell-nonspecific effects, 169
cellular targets, mechanisms of action, selectivity for thin sensoryneurons, 143
differences in sensitivity, mammalian species, 166
interaction with nerve growth factor, 184
intermediate effects, mammalian sensory neurons, 150
intracerebroventricular application, 163
-like substances, 186long-term neurotoxic effects, mammalian sensory neurons, 151mechanisms of action, 170
mechanisms of cell-nonselective effects, 187
ontogenetic shift in neurotoxicity, rat, 186periaxonal administration, 160
pharmacological tool, 189pharmacological tool (table), 190
primary afferent neurons, markers (table), 146resiniferatoxin and, chemical structure (fig.), 145
routes of administration, 190ruthenium red as functional antagonist, 182
selectivity of action, 155, 158, 160
sensitivity, age and strain differences, mammalian species, 167
sensory neurons in culture, 165
sensory neurons in vitro, 165
systemic
adult mammals, 156, 160newborn mammals, 151
targets and selectivity
excitable cells, mammals (table), 148
excitatory action, 147
topical administration, specific brain regions, 164
Capsaicinoids
desensitizing and neurotoxic effects, structure-activity relationships,
171
excitatory effect, structure-activity relationship, 170
Capsozepine, competitive antagonist of capsaicin, 173
Cardiovascular system
corticotropin-releasing factor regulation, autonomic function, other
peripheral actions, 446
inhibition of nitric oxide synthesis, 114regulation, 5-HT neurons, 573
serotonin-selective arylpiperazines, 527
Casein kinase, DARPP-32 cells, 311
Catalepsy, neuroleptic-induced, effect of serotonin, 595
Catecholamines
binding studies, 256false neurotransmitter hypothesis, 39
a-receptor, 255
a-receptor, 284structure-activity relationships, 256
uptake and metabolism, 257
Central nervous system
localization of corticotropin-releasing factor, 428
neuroanatomical relationship, serotonergic and dopaminergic sys-
tems, 589
nitric oxide, 122
Cerebellum
basic circuitry diagram (fig.), 4
cell fractions, 4
cyclic GMP and, motor activity, dopaminergics (table), 3
drug effects on cerebellar cGMP (table), 7
pharmacology of cyclic guanosine 3’,5’-monophosphate, 1
slices, 4
Cerebrospinal fluid
corticotropin-releasing factor concentrations, 458
schizophrenia (fig.), 459
endocrine studies and, anorexia nervosa, 4605-hydroxyindoleacetic acid, 511
Chloride channel, regulation, cystic fibrosis, 329
6-Chloro-2-(l-piperazinyl)pyrazine, studies in humans, 539
m-Chlorophenylpiperazine
food intake, 534
locomotor activity, 536
neuroendocrine measures, 535
other substituted phenylpiperazines and, 529
patients with neuropsychiatric disorders, 530
related piperazines and, in vitro and in animals, 532
temperature, 534
Chlorpromazine, pED�o (table), 594Cholecystokinin peptides, cerebellar cGMP (table), 9
Cholinemodulators, 18
serotonergic interactions, 520
Cholinergics, cerebellar cGMP (table), 8
Circadian rhythm
corticotropin-releasing factor regulation, neuroendocrine function,
435
sleep-wake-arousal cycle, 564Cirrhosis, amelioration of hepatic encephalopathy (fig.), 59
Citrulline, synthesis from L-arginine, Ca’� dependence, nitric oxide
(fig.), 123
Climbing fiber system, cGMP in the cerebellum, 15
Clozapineatypical antipsychotic drugs, 588pED� (table), 594
pK1 values (table), 592
Coccaro, Emil F. See Siever et al., 509Collagen, blood platelet receptors, 271
Convulsants, cerebellar cGMP (table), 10
Coronary vessels, nitrate esters, 380
Corticotropin-releasing factor
administration
gastrointestinal responses, 447
metabolic responses, 447
analgesic and anti-inflammatory properties, 445
autonomic actions (fig.), 446binding in rat olfactory bulb membranes, 433
cerebrospinal fluid concentrations, 458concentrations, alprazolam and stress (fig.), 455
concentrations and receptors, Alzheimer’s disease, 460
-containing neurons and receptors, 428
electrophysiological responses, 451
historical perspectives, 426
hypersecretion, pathophysiology, psychiatric illness, 457
hypophysiotropic system, ontogeny of, 435
infusion, animals in darkened compartment (fig.), 450
-like immunoreactivity, receptor binding, Alzheimer’s disease (fig.),
460
local gonadal actions, 448
localization in peripheral tissues, 430localization of messenger RNA, 432
messenger RNA, insulin-induced hypoglycemia (fig.), 441
608 INDEX
neurons
actions of cytokines, 444
effects of stress, 453extrahypothalamic, miscellaneous changes, 456
extrahypothalamic, pharmacological manipulation, 454
feedback and stress-induced effects, 439
nonhypophysiotropic, pharmacological and environmental pertur-
bation, 453other endocrine functions, 441
responses, miscellaneous manipulations, 442
peptide and messenger RNA localization, 428physiology and pharmacology, 425
pituitary corticotrophs, 436
potentiation of action on corticotroph, 437pressure application, different neurons (fig.), 451
receptors, 433
anterior pituitary, feedback- and stress-induced effects, 441
regulation
autonomic function, other peripheral actions, 446
behavior, laboratory animals, 448immune function, 444
neuroendocrine function, 435
neuron, neurotransmitter regulation, 437
reproductive hormone function, 442
-stained cell groups and fiber systems, rat brain (fig.), 429
stimulation test, 457
Corticotropin-releasing hormone, gene, structural organization, rat
(fig.), 433
Cusack, Noel J. See Hourani and Cusack, 243
Cyclic AMP, contractile force, time course ofeffects, isoprenaline (fig.),
209
Cyclic GMP
action of organic nitrate esters, 357
cerebellarantagonism by drugs (table), 15
drug and behavioral effects, stress, 3
drug effects (table), 7
modulation, NO synthetase inhibitor (table), 14changes in motor activity, dopaminergics (table), 3confounding variables, 2
-dependent protein kinase, 306diagram of basic components (fig.), 357lesions and mutant mice, 2
logit-log dose-response curves, CPP and tiletamine (table), 14
microwave tissue fixation, 2
mouse cerebellar, antagonists, EAA-dependent increases (table), 15
organic nitrate esters, cellular calcium homeostasiS, 363
pharmacology of, cerebellum, 1
relation to mode of action, organic nitrate esters, 359
routes of drug administration, 2
schematic drawing showing cellular mechanisms, mediation, vascular
smooth muscle relaxation (fig.), 365
tissue microdissection, 2
Cycloheximide
dexamethasone and, induction, nitric oxide synthase (fig.), 132
L-NIO and, time-dependent loss of tone, aorta (fig.), 130
Cystic fibrosis, chloride channel regulation, 329
Cytokines, actions on hypothalamic corticotropin-releasing factor neu-rons, 444
Denopamine, beta adrenoceptors, 214
Depressants, cerebellar cGMP (table), 10
Depression
animal models, 449, 544anxiety and, animal models, 537major
corticotropin-releasing factor hypersecretion, 457
signs and symptoms (table), 451
studies of azapirones, 542
studies of m-chlorophenylpiperazine, 531
N-Desmethyldiazepam
diazepam and (fig.), 51
summary of levels (fig.), 53
De Wied, David. See L#{225}zl#{243}et al., 73
Dexamethasone
contitutive and inducible nitric oxide synthases, rat aorta (fig.), 132
cycloheximide and, induction, nitric oxide synthase (fig.), 132
DiazepamN-desmethyldiazepam and (fig.), 51
summary of levels (fig.), 53
Diet, hepatic encephalopathy, 55
Dihydroergotamine, sumatriptan interactions, neurotransmitter recep-
tor (table), 581
DNA
a,-adrenoceptor, 498cloning of a,-adrenoceptor, 493
DNA, complementary
a1-adrenoceptor, functional expression, 495
a�pha-2 adrenoceptor cloning, 496Dobutamine
beta adrenoceptors, 214
left ventricular dP/dT, dilated cardiomyopathy (fig.), 230
peak positive left ventricular dP/dT (fig.), 223
Dopamine
beta adrenoceptors, 214
mechanism of action of antipsychotics, 588-mediated behavior, mesolimbic pathway, effect of serotonin, 597mesolimbic pathways, effect of serotonin, 597
modulators, 16regulation of natriuresis, 330
serotonergic regulation, 595
serotonin and, 520
neuroanatomical relationship, 589
Dopaminergics, changes in motor activity, cerebellar cGMP (table), 3
Dopexamine, beta adrenoceptors, 214Drug discrimination
animal models, anxiety and depression, 544
anxiety and depression, animal models, 537
EAA, -dependent increases, antagonists, mouse cerebellar cGMP levels
(table), 15
EAA agonists, antagonists and, Cerebellar cGMP (table), 11
Edema, cerebral, prevention of hyponatremia, V2 antagonists, 88
Electroencephalography, convulsive studies and, 452
Electrophysiology
m-chlorophenylpiperazine, 533
mesolimbic dopamine pathways, effect of serotonin, 597
responses to corticotropin-releasing factor, 451
serotonergic regulation, dopaminergic function, 595Emesis, 5-HT3 receptor agents, 582
Encephalopathy
hepaticamelioration (fig.), 59
animal models, 34
behavioral characteristics of rabbit (table), 34benzodiazepine ligands, rat brains (fig.), 50benzodiazepine ligands (fig.), 49
benzodiazepine receptor ligands (fig.), 46
benzodiazepine receptor ligands, 48
chronic, 54
clinical manifestations, 29
clinical stages (table), 30
complications of liver disease, 54
definition, 28development of, traditional concepts (fig.), 33
INDEX 609
electrophysiology, 31
GABA/benzodiazepine receptor complex, 42
improvement of hepatocellular function, 54
insufficiency and vascular rearrangement (fig.), 29
metabolites found in abnormal levels (table), 34
neuropathology, 30
pathogenesis and treatment, 27
precipitating factors, 53proposed mechanisms of pathogenesis, 32
reduction, portal-systemic shunting, 54
therapeutic modalities, 53, 54
Endothelial cells, Ca2�-independent nitric oxide synthase, time course
of induction (fig.), 129
Endothelium, interaction with organic nitrate esters, 370
Endothelium-derived relaxing factor
controversy about chemical identity, 112
identification as nitric oxide, 111nitric oxide and, comparison of stability (fig.), 112
Enzyme, activation, capsaicin, 177
Epinine, beta adrenoceptors, 214
Ethanol
cGMP in the cerebellum, 12
corticotropin-releasing factor, actions on HPA axis, 443
-induced gastric lesions, plasma AVP (fig.), 87
Ethylene glycol dinitrate, concentration-effect curve (fig.), 355
Exercise, pharmacokinetics of glyceryl trinitrate, 373
Fatty acids, central nervous system electrical activity, 39
Fenfluramine
neuroendocrine responses, 512
responses, extrahypothalamic corticotropin-releasing factor neurons,
454Fibroblasts, generation of nitric oxide, 130
Flumazenil
antagonist to benzodiazepine, 57efficacy in clinical trials (table), 59
pharmacological properties, 58
potential clinical use, 58remission of chronic intractable PSE (fig.), 60
Fluperlapine
pED� (table), 594
pK1 values (table), 592
Fluphenazine, pED� (table), 594
Fornal, Casimir A. See Jacobs and Fornal, 562
Forskolin, heart rate response to increasing doses, bolus injections
(fig.), 224
GABAergic agents, cerebellar cGMP (table), 9
GAP-43, phosphorylation by Ca2� influx, 318
Gastric circulation
mucosa, V, antagonist (fig.), 86
role of vasopressin, cytoprotection (fig.), 86
vasopressin antagonists, 84
Gastrointestinal system, corticotropin-releasing factor administration,
447
Gene, corticotropin-releasing hormone, structural organization, rat
(fig.), 433
Genetic disorders, role of corticotropin-releasing hormone, animal
models, 443Glucocorticoids, immunologically induced formation, nitric oxide, 131Glucose
DRN 5-HT neuron and cortical EEG (fig.), 572
implication of brain 5-HT, 571
Glyceryl trinitrateabsorption and bioavailability, 374
analysis of, 371
analytic methods for GC determination (table), 372buccal and oral, tolerance development, 393
concentration-effect curve (fig.), 355
Congestive heart failure, 389
distribution, 374handling of samples, 372
influence of posture, 373
influence of sampling site, 372intravenous, tolerance development, 392
invention of, 353
isoprenaline and, induced hypotension, effect of L-NIO (fig.), 119lactate production, ventricular heart muscle (fig.), 363
metabolism and elimination, 375
ointment and patches, 393
oxygen consumption, ventricular heart muscle (fig.), 366
pharmacokinetic data, 374
pharmacokinetics, effect of exercise, 373
pharmacokinetic studies, 370
relaxant effect on blood vessels (table), 355
route of administration, 373
sorption to materials, 370
stable angina pectoris, 382
tolerance development, 392Glycine, NMDA-associated agonists, 13
Glycogen synthase kinase 3, regulation of cell-cell interactions, 311
Gonads, local actions, corticotropin-releasing factor, 448
G-proteins
a-adrenoceptor function, 490
-coupled receptor proteins, schematic model (fig.), 494
-coupled receptors, 321
ventricular
adenylate cyclase activation, myopathy (table), 218adenylate cyclase activation, end-stage 1CM (table), 221
Granisetron
antiemesis, 582clinical status (table), 583
Greengard, Paul. See Walaas and Greengard, 299
Growth hormone, secretion, corticotropin-releasing factor neurons, 441Guanylate cyclase
characteristics of Nervous and Weaver mice (table), 3
proposed scheme for NMDA augmentation (fig.), 21
soluble, trasduction mechanism, nitric oxide, 110
Guinea pig, long-term neurotoxic effects, capsaicin, mammalian sen-
sory neurons, 159
Haloperidol, pED,o (table), 594
Heart
aortic valve disease, 223
atrial tissues, positive inotropic effects, 209
autonomic actions, corticotropin-releasing factor (fig.), 446
biventricular failure, ventricular beta adrenoceptors, subtype distri-
bution (table), 218
chronic failure, alterations, beta adrenoceptors, 223
circulation, vasopressin antagonists, 81
congestive failure, nitrates, 389
dilated cardiomyopathy, dobutamine, left ventricular dP/dT (fig.),
230
end-stage dilated cardiomyopathy, ventricular G proteins (table), 218
end-stage isehemic cardiomyopathy, 220
ventricular G proteins (table), 221
failing, beta adrenoceptors, 216failure, beta adrenoceptors (fig.), 217
human
beta adrenoceptors, 203
effects of drugs, beta adrenoceptors, 228
hypertrophic obstructive cardiomyopathy, 223
idiopathic dilated cardiomyopathy, 217
left ventricle, density, beta adrenoceptors (fig.), 225
left ventricular membranes
antagonism of stimulation, beta adrenoceptors (fig.), 208
610 INDEX
determination, beta adrenoceptors (fig.), 205
mitral valve disease, 221
myocardial beta adrenoceptors, subtype distribution (table), 222nonfailing
beta adrenoceptors, 205numbers of beta adrenoceptors, subtype distribution (table), 206
nonfailing or end-stage DCM, maximal positive inotropic effects,
beta adrenoceptors (fig.), 220peak positive left ventricular dP/dT, dobutamine or calcium gluco-
nate infusion (fig.), 223right atria
beta adrenoceptor antagonists (fig.), 229isoprenaline-induced positive inotropic effect (fig.), 210
procaterol and noradrenaline (fig.), 229spare receptors, beta adrenoceptor agonists, 224
tetralogy of Fallot, 223
transplanted human, beta adrenoceptors, 226Vi antagonist, perfusion pressure changes (fig.), 82
vasoconstriction, vasopressin analogues (fig.), 82
ventricular muscle, lactate production, glyceryl trinitrate (fig.), 363
ventricular tissues, 210
Heart rate
DRN 5-HT neuron (fig.), 574
firing rate of DRN 5-HT neurons (fig.), 570
isoprenaline-induced increases (fig.), 212
response to bolus injections, isoprenaline and forskolin (fig.), 224
Hemodynamics, peripheral, nitrate esters, 378
Heparin, drug interactions, nitrates, 406
Hepatocytes, Kupffer cells and, nitric oxide, 129
Hieble, J. Paul. See Ruffolo et al., 475
Higgs, E. A. See Moncada et al., 109
Histaminemechanism of action of antipsychotics, 588nitric oxide, 124
Holzer, Peter. Capsaicin: Cellular targets, mechanisms of action, andselectivity for thin sensory neurons, 143
Hourani, Susanna M. 0. and Noel J. Cusack. Pharmacological receptorson blood platelets, 243
HP-370, pED,�o (table), 5945-Hydroxyindoleacetic acid
cerebrospinal fluid, 511
patients with affective and personality disorders, 515receptor subtypes, 515
5-Hydroxytryptamine
binding studies and receptor isolation, 259structure-activity relationships, 258
uptake and metabolism, 259Hypertension, DRN 5-HT neuron (fig.), 575
Hypoglycemia, insulin-induced, corticotropin-releasing factor mRNA
(fig.),441
Hyponatremia, cerebral edema and, prevention of, V2 antagonists, 88Hypotension, induced by isoprenaline and GTN, effect of L-NIO (fig.),
119
IC! 204,636, cortical 5-HT, and striatal pK values (table), 593ICS 205-930, antiemesis, 582N-Iminoethyl-L-ornithine
cycloheximide and, time-dependent loss of tone, aorta (fig.), 130hypotension induced by isoprenaline and GTN (fig.), 119platelet anti-aggregatory activity (fig.), 126
Imipramine, binding with platelets, 512Immune function, regulation, corticotropin-releasing factor, 444
Indole, modulators, 19
Insulin
DRN 5-HT neuron and cortical EEG (fig.), 572-induced hypoglycemia, corticotropin-releasing factor mRNA (fig.),
441
Interferon-’y, Ca2�-independent nitric oxide synthase, time course of
induction (fig.), 129
Ion channelsregulation, 322
regulation following intracellular injection, protein kinases, nerve
cells (table), 323
lonophores, GABA/BzR/chloride, supramolecular complex (fig.), 42
Ipsapirone, single-dose studies in humans, 541
Isoprenaline
contractile force and cAMP (fig.), 209GTN and, induced hypotension, effect of L-NIO (fig.), 119
heart rate response to increasing doses, bolus injections (fig.), 224
-induced increases in heart rate (fig.), 212
-induced positive inotropic effect, right atria (fig.), 210-induced stimulation of left ventricular adenylate cyclase, antago-
msm, beta adrenoceptors (fig.), 208
percentage of receptor occupancy, positive inotropic effect (fig.), 226
Isosorbide dinitrate
absorption and bioavailability, 376
distribution, 377isosorbide-5-mononitrate and
congestive heart failure, 389pharmacokinetic data, 376
stable angina pectoris, 384metabolism and elimination, 377
tolerance development, 394isosorbide-5-mononitrate, tolerance development, 394
Jacobs, Barry L. and Casimir A. Fornal. Activity of brain serotonergicneurons in the behaving animal, 562
Jones, E. Anthony. See Basile et al., 27
Kahn, Ren#{233}S. See Siever et a!., 509
Kainate, low-dose response curves, mouse cerebellar cGMP (fig.), 13
Kidney
alpha-2 adrenoceptor, primary structure (fig.), 497
autonomic actions, corticotropin-releasing factor (fig.), 446hemodynamic changes, V, antagonist (fig.), 84
Kupffer cells, hepatocytes and, nitric oxide, 129
Lactuloase, related carbohydrates and, hepatic encephalopathy, 56L#{225}szl#{243},Ferenc, Jr. See IAzl#{243}et al., 73
LIszl#{243},Ferenc A., Ferenc L#{224}sl#{243},Jr., and David De Wied. Pharmacology
and clinical perspectives of vasopressin antagonists, 73
Lawlor, Brian A. See Siever et al., 509
Lawrence, Timothy L. See Siever et al., 509Lergotrile, changes in motor activity, cerebellar cGMP (table), 3
Leech, K. P. See Murphy et al., 527
Ligandsbenzodiazepine
hepatic encephalopathy, rabbits (fig.), 49
hepatic encephalopathy, rat brains (fig.), 50
summary of levels (fig.), 53benzodiazepine receptor
hepatic encephalopathy, 27open field performance, hepatic encephalopathy (fig.), 46
sigma, 14Lipopolysaccharide, Ca2�-independent nitric oxide synthase, time
course of induction (fig.), 129
Liver, nitric oxide synthase activity, lipopolysaccharide (fig.), 131Locomotion
azapirones, 544m-chlorophenylpiperazine, 535
Long-term potentiation, regulation of, 327Loxapine, pED� (table), 594
Macrophages
effect of L-NMMA (fig.), 128synthesis of nitric oxide, 124
INDEX 611
Mammalsadult, systemic capsaicin, 156differences in sensitivity
age and strain differences, 167
capsaicin, 166
newborn, systemic capsaicin, 151, 155, 157MAP-2, phosphorylation, 332
MARCKS protein, phoaphorylation, 317
Mass spectrometry, 15N0 release from porcine aortic endothelial cells
(fig.),114
MDL 72222, clinical status (table), 583Melperone
pEDs4� (table), 594pK1 values (table), 592
Meltzer, Herbert Y. and J. Frank Nash. Effects of antipsychotic drugs
on serotonin receptors, 586
Mental illness, neuropeptide therapy, 4611-(2-Methoxyphenyl)piperazine, studies in humans, 540
N-Methyl-D-aspartate
-associated glycine agonists, 13-associated glycine receptor antagonists, 14
augmentation, proposed scheme (fig.), 21
low-dose response curves, mouse cerebellar cGMP (fig.), 13
Methylphenidate, changes in motor activity, cerebellar cGMP (table),3
Metoprolol, 6 months treatment, beta adrenoceptor density, heart (fig.),
230Mice
characteristics of Nervous and Weaver strains (table), 3
mutant, cyclic GMP, 1Microtubule proteins, phosphorylation, 331
Migrainebulimia and, 532
sumatriptan, 579Moncada, S., R. M. J. Palmer, and E. A. Higgs Nitric oxide: Physiology,
pathophysiology, and pharmacology, 109Monoaminergic agents, cerebellar cGMP (table), 7N-Monomethyl-L-arginine, modulation of cerebellar cGMP, NO syn-
thetase inhibitor (table), 14
NG�Monomethyl.L.arginine
changes in blood pressure (fig.), 117
effect on aortic pressure (fig.), 116
leishmanicidal activity, activated macrophages (fig.), 128
platelet anti-aggregatory activity (fig.), 126
Morphine
response of single NRM 5-HT neuron (fig.), 569tail-flick test, NRM 5-HT neurons (fig.), 567
Mossy fiber system
anatomy/neurochemistry, 16
pharmacology, 16
polysynaptic circuitry (fig.), 17
Murphy, D. L., K. P. Leach, C. S. Aulakh, and T. A. Pigott. Serotonin-
selective arylpiperazines with neuroendocrine, behavioral, tern-perature, and cardiovascular effects in humans, 527
Muscimol, Purkinje neuron responses (fig.), 44
Muscle, smoothsumatriptan effects, 580vascular
cellular mechanisms, cyclic GMP (fig.), 365
cyclic GMP system, organic nitrate esters, 359
hyperpolarization, 366relaxant action, organic nitrate esters (fig.), 370
Myelin basic protein kinase, phosphorylation, 311
Myocardial infarctionglyceryl trinitrate, 388unstable angina, 387
Myocardial isehemia, unstable angina, 387
Myocardium, cyclic GMP system, organic nitrate esters, 359
Nash, J. Frank. See Meltzer and Nash, 586
Natriuresis, dopaminergic regulation, 330
Nemeroff, Charles B. See Owens and Nemeroff, 425
Nerve
alveolar, stimulation, NRM 5-HT neurons (fig.), 569conduction, blockade of, 151
neurogenic inflammation, 581Nerve cells
functional importance, second messenger-regulated protein kinases,
305
regulation of ion channels, intracellular injection, protein kinases
(table), 323Nerve growth factor, interaction with capsaicin, 184Nerve terminal
phosphoproteins, presynaptic receptors, 319
protein phosphorylation, depolarization-induced Ca’� influx (table),
316
Nervous system, function, protein kinases (table), 304
Neuritic plaques, fl-amyloid precursor protein phosphorylation, 333
Neurochemistry, m-chlorophenylpiperazine, 533
Neuroendocrine function, corticotropin-releasing factor regulation, 435
Neuroendocrinology, m-chlorophenylpiperazine, 535Neurofibnillary tangles, tau factor phosphorylation, 332
Neurofilament proteins, phosphorylation, 331Neurons
afferent, central endings, capsaicin administration, 163
capsaicin-sensitive, 169
corticotropin-releasing factor
actions of cytokines, 444distribution, 428
effect of pressure application (fig.), 451
effects of stresa, 453
extrahypothalamic, pharmacological manipulation, 454
feedback and stress-induced effects, 439
nonhypophysiotropic, pharmacological and environmental pertur-
bation, 453
other endocrine functions, 441regulation, 437
responses, miscellaneous manipulations, 442
DRN 5-HT
cortical EEG (fig.), 572
firing rate, heart rate (fig.), 570heart rate and blood pressure (fig.), 574
5-HT1A agonist (fig.), 576hypertension, hypotension (fig.), 575
peak elevation of brain temperature (fig.), 572physiological responses (fig.), 570quiet waking, feeding and active waking (fig.), 576respiratory rate, heating trial (fig.), 571
sleep-wake cycle (fig.), 565
stress, 568
suppression, orientation to opening the door (fig.), 576waking, sleep (fig.), 577
function, protein phosphorylation, 299
5-HT
cardiovascular regulation, 573
mean discharge rates (fig.), 566lack of sensitivity, neurotoxic action, capsaicin, 169
mammalian sensory, acute excitatory effects, capsaicin, 146
NCS 5-HT, transition from REM sleep to wakefulness (fig.), 566
NRM 5-HTalveolar nerve stimulation (fig.), 569
extracellular action potential (fig.), 564mean discharge rate (fig.), 568tail-flick trials (fig.), 567
primary afferent
capsaicin, acute and long-term effects (table), 148
capsaicin actions, 145
612 INDEX
markers, capsaicin sensitivity (table), 146
secondary changes in pathways, 154
sensorycapsaicin, long-term neurotoxic effects, 151
consequences of excitation, 149
culture, capsaicin, 165
intermediate effects, capsaicin, 150
in vitro, effects of capsaicin, 165mechanisms of action, 188
mechanisms of selective effects, 174
peripheral endings, capsaicin administration, 164peripheral endings, capsaicin action, 184
serotonergic, behaving animal, 563
thin sensory, capsaicin, 143Neuropeptides, therapy of human mental illnese, 461
Neuropeptide Y, corticotropin-releasing factor, actions on HPA axis,
443
Neuropsychiatric disorders
overview, 510
serotonin and, 507
serotonin receptor subtypes, 579
studies of azapirones, 542
studies with m-chlorophenylpiperazine, 530
Neurotoxins, synergism, 38, 39Neurotransmitter
developing systems, interactions, 557excitatory amino acid, 40
“false”, branched-chain and aromatic amino acids, 37
interaction, serotonin, 516
liver failure, 39mechanism of action, antipsychotics, 588
pathways, regulation of interactions, 325
regulation of corticotropin-releasing factor, 437
regulation of synthesis, tyrosine hydroxylase, 314
release, synapsins, 314
synthesis and release, phosphoproteins, presynaptic function, 314Neutrophils, nitric oxide, 128
Nichols, Andrew J. See Ruffolo et al., 475
Nitrate esters
coronary vessels, 380in vitro evaluation of effects, 354
in vivo evaluation of effects, different target organs, 378
mode of action, cyclic GMP, 359
organic
arachidonic acid metabolites, 366
chemical structure (fig.), 353
clinical use, mechanisms of actions, 351
cyclic GMP, cellular calcium homeostasis, 363
explanation of tolerance (fig.), 401
interaction with endothelium, 370
mechanism of, 398
other suggested mechanisms, 365pharmacokinetics, 370
proposed mechanism of action, cellular level, 357
relaxant action, vascular smooth muscle (fig.), 370
tissue biotransformation, 367
relaxant effect, regional and species differences, 355
vasodilatory effects, 356
Nitrates
airway diseases, 391
dependency, 404clinical problem, 404
mechanism of, 404
drug interactions, 406miscellaneous therapeutic uses, 391
noncardiovascular uses, 391
organic
clinical therapeutic use, 382cross-tolerance, 397
differences between different target organs, 397
tolerance development and dependency, 392peripheral vascular diseases, 391
relationship between pharmacokinetics, therapaeutic effects, 377side effects, 407
Nitric oxide
Ca2� dependence, citrulline synthesis from L-arginine (fig.), 123
effector molecule, immunological reactions, 124endothelium-derived relaxing factor, 111
immunologically induced formation in vivo, 130
inhibition by glucocorticoids, 131
inhibition of synthesis, cardiovascular system, 114
measured by bioassay and by chemilumineseence, 111
novel inhibitors, 116pathological implications, 118pharmacological actions, 120
pharmacological and physiological implications, 117
physiology, pathophysiology, pharmacology, 109physiology and pathophysiology of synthesis, 126release from porcine aortic endothelial cells, mass spectrometry (fig.),
114
synthesis, 114, 120
L-arginine, platelet aggregation (fig.), 121
macrophages, 124transduction mechanism, soluble guanylate cyclase, 110
Nitric oxide synthase
activity in rat liver, lipopolysaccharide (fig.), 131Ca2�-independent (fig.), 129characteristics, 125constitutive and inducible, effect of dexamethasone, rat aorta (fig.),
132induction, effect of cycloheximide, dexamethasone (fig.), 132
similarities and differences, constitutive and inducible groups (table),
126NG.Nitro.L�arginine methyl ester, changes in blood pressure (fig.), 117
Nitroprusside, chemical structure of organic nitrate esters (fig.), 353
Nociception538
tail-flick test, NRM 5-HTneurons (fig.), 567Noradrenaline
-induced positive inotropic effects, left papillary muscles (fig.), 211
-induced stimulation of left ventricular adenylate cyclase, antago-nism, beta adrenoceptors (fig.), 208
Noradrenergic modulators, cGMP in the cerebellum, 20
Noradrenergic system, function of, 514
Norepinephrine, mechanism of action of antipsychotics, 588
Obsessive-compulsive disorder, studies of m-chlorophenylpiperazine,
530Olfactory bulb, rat membranes, corticotropin-releasing factor binding,
433
Ondansetron, antiemesis, 582Opiates
cerebellar cGMP (table), 8
cGMP in the cerebellum, 19ORG 5222, cortical 5-HT2 and striatal pK1 values (table), 593Owens, Michael J. and Charles B. Nemeroff. Physiology and pharma-
cology of corticotropin-releasing factor, 425
Oxygen consumption, effect of glyceryl tninitrate, ventricular heartmuscle (fig.), 366
Palmer, R. M. J.. See Moncada et al., 109
Panic disorder, studies of m-chlorophenylpiperazine, 530Pentaerythreitol tetranitrate, chemical structure of organic nitrate
esters (fig.), 353Peptide, release, capsaicin, 177
INDEX 613
Peripheral tissues, localization of corticotropin-releasing factor, 430
Perlapine, pK1 values (table), 592Peroutka, Stephen J. Serotonin receptor subtypes and neuropsychiatric
diseases: Focus on 5-HT1D and 5-HT3 receptor agents, 578
Pharmacology, developmental, 553, 558
Phenols, liver enzymes, 39
Phenylpiperazines
m-chlorophenylpiperazine, 529substituted, studies in humans, 539
Phosphatidylinositol, turnover, cyclic nature (fig.), 484
Phosphodiesterase inhibitors, beta adrenoceptors, 231
Phospholipid, metabolism, 484
Phosphoprotein phosphatases, brain, 312
Phosphoproteins
clinical disorders and, 328
nerve terminal, presynaptic receptors, 319
postsynaptic function, 319presynaptic function, 314
Phosphorylase kinase, brain, 309Pigott, T. A. See Murphy et a!., 527
Pipamperone, pK1 values (table), 592Piperazines, m-chlorophenylpiperazine, in vitro and in animals, 532
Piribedil, changes in motor activity, cerebellar cGMP (table), 3
Pitressin, serum sodium level, V, antagonists (fig.), 89
Pituitary
anterior, corticotropin-releasing factor receptor, feedback- and
stress-induced effects, 441localization, corticotropin-releasing factor receptors, 433
Plasma membrane, receptors, regulation, protein phosphorylation (ta-
ble), 320Platelet-activating factor
binding studies and receptor isolation, 269
blood platelet receptors, 267
structure-activity relationships, 268uptake and metabolism, 270
Platelets
aggregation, L-arginine, nitric oxide synthesis (fig.), 121
anti-aggregatory activity, effect of L-NIO, L-NMMA (fig.), 126cyclic GMP system, organic nitrate esters, 359
-imipramine binding, 512in vivo evaluation of effects, nitrate esters, 381pharmacological actions of nitric oxide, 120pharmacological receptors, 243
responses, 245serotonin uptake, 512stimulus-response coupling, 247structure and function, 244
Polyamines, antagonism, effects of NMDA, quisqualate receptor acti-vation, 14
Posture, influence on glyceryl trinitrate, 373
Potassium channelactivation, 366nerve cells, 323
Practolol, propranolol or, salbutamol-induced tachycardia (fig.), 213Prenalterol, beta adrenoceptors, 214Prolactin, secretion, atypical antipsychotic drugs, 588
Pro-opiomelanocortin, corticotropin-releasing factor regulation, neu-roendocrine function, 435
Propranolol
atenolol and, tachycardyia (fig.), 212
practolol or, salbutamol-induced tachycardia (fig.), 213
Prostaglandins
Na�/W exchange, alpha adrenoceptors, platelets (fig.), 488structure-activity relationships, 280
thromboxane and, 262Protein
phosphorylationbrain, first messengers (table), 301
functional importance, 300neuronal, multiple sites (table), 302
neuronal function, 299
systems, 301Protein kinases
activation by second messengers, 303
brain, 302
Ca’�/calmodulin-dependent, 306, 308
Ca’�/phospholipid-dependent, 309
cyclic GMP-dependent, 306cyclic nucleotide-dependent, 303
general mechanisms for activation, 302
nervous system function (table), 304
neurofilament, 311
regulation of ion channels (table), 323
second messenger-independent, 311
second messenger-regulated, 303tyrosine-specific, 311
Protein phosphatasesserine/threonine-specific (table), 312
tyrosine-specific, 313
Protein phosphorylationAlzheimer’s disease, 331
depolarization-induced Ca’� influx, nerve terminals (table), 316regulation of plasma membrane receptors (table), 320
Protooncogenes, tyrosine-specific protein kinases, 311
Psychiatric disorders, role of serotonin, 509
Psychiatric illness, pathophysiology, corticotropin-releasing factor hy-
persecretion, 457Psychiatry, serotonin function, 516
Purkinje neuronsdifferential sensitivity (fig.), 45
responses, rate meter records, muscimol (fig.), 44
responses to Ro 14-7437 (fig.), 45
Pyrogen, activity of DRN-5HT neuron (fig.), 571
Pyruvate dehydrogenase kinase, activation in brain, 311
Quipazine, studies in humans, 540
Quisqualate, low-dose response curves, mouse cerebellar cGMP (fig.),
13
Raclopride, pED,o (table), 594
Radioligands, beta-adrenoceptor antagonist (table), 205
Ratlong-term neurotoxic effects, capsaicin, mammalian sensory neurons,
151, 160
ontogenic shift in neurotoxicity, capsaicin, 186
Receptorsadenosine, agonists and antagonists (fig.), 276
adenosine A2, characteristics, Nervous and Weaver mice (table), 3
adenosine 5’-diphosphate
agonists (fig.), 251
antagonists (fig.), 252
affinity profile
azapirones, 543
second messenger system effects, 532
alpha, catecholamines, 255
benzodiazepine
antagonists, 57
GABA, hepatic encephalopathy, 42
ligands, hepatic encephalopathy, 27, 48
ligands (fig.), 46
modulators, 5
beta, catecholamines, 284
blood platelets, 243cholecystokinin, modulators, 18
corticotropin-releasing factor, 433
anterior pituitary, feedback- and stress-induced effects, 441
614 INDEX
biochemical characterization, 433
CRF-like immunoreactivity (fig.), 460
distribution, 428
localization, 433localization, pituitary and brain, 433signal transduction, second messenger systems, 434
excitatory amino acid, modulators, 12
GABA, organization and function, 41
GABAA, protein phosphorylation, 320GABAB, agonists, 6
G-protein coupled, 321
schematic model (fig.), 494
growth factor, 312
5-HT,
down-regulation, 594pK1 values, atypical psychotics (table), 592
5-HT,, 582agents (table),583
antagonism, antipsychotic drugs, 598a,mputational model (table), 584
5-HT1A, azapirones, 5415-hydroxyindoleacetic acid, subtypes, 515
influence on development, 555intracellular, 322
ion channel-coupled, 319
isolation, binding studies, 5-hydroxytryptamine, 259
muscarinic acetylcholine, 321
neurotransmitter
DHE and sumatriptan interactions (table), 581serotonin, brain development and pharmacology, 553
nicotinic acetylcholine, 319
occupancy, positive inotropic effect, isoprenaline (fig.), 226plasma membrane, regulation, protein phosphorylation (table), 320
platelet-activating factor, agonists and antagonists (fig.), 268
platelet (fig.), 283
platelet (table), 282
presynaptic, nerve terminal phosphoproteins, 319
programmable, 555prostaglandin, agonista (fig.), 281
regulation of function, 319
serotonin, see also 5-HTagonists, neuroendocrine responses, 513
antagonism, atypical antipsychotics, 598
binding properties of antipsychotics, 592effects, antipsychotic drugs, 587
“families”, 590physiological effects, 543
subtypes, 591
subtypes, neuropsychiatric diseases, 579
subtypes, physiological effects, 534spare, beta adrenoceptor agonists, heart, 224
stimulatory agonists, adenosine 5’-diphosphate, 250
target tissues, 556
thromboxane A2, agonists and antagonists (fig.), 263
tyrosine kinase-coupled, 322vasopressin, subtypes, antagonists, 92
Renzapride, antiemesis, 582Reproductive hormone, function, corticotropin-releasing factor, 442
Reserpine, corticotropin-releasing factor, actions on HPA axis, 443
Resiniferatoxin
capsaicin and, chemical structure (fig.), 145
potent capsaicin agonist, 171
Respiration
activity of DRN 5-HT neurons (fig.), 571depression, cGMP levels, 3
Rilapine, pK1 values (table), 592
Risperidone
cortical 5-HT, and striatal pK1 values (table), 593pED�,o (table), 594
RMI-81582, pK1 values (table), 592
RNA, messengercorticotropin-releasing factor peptide, 428corticotroptin-releasing factor, insulin-induced hypoglycemia (fig.),
441localization of corticotropin-releasing factor, 432
RO 363, beta adrenoceptors, 214
Ro 14-7437, Purkinje neuron responses (fig.), 45
Ruffolo, Robert R., Jr., Andrew J. Nichols, Jeffrey M. Stadel, and J.Paul Hieble. Structure and function of a-adrenoceptors, 475
Ruthenium red, functional antagonist of capsaicin, 182
SCH 23390, pK1 values (table), 592
Schizophrenia
cerebrospinal fluid CRY-like immunoreactivity (fig.), 459mechanism of action of antipsychotics, 588serotonin, 519
studies of m-chlorophenylpiperazine, 531Serine
protein phosphatases, 312protein phosphatases in brain (table), 312
Serotonin
Alzheimer’s disease, 519
cholinergic interactions, 520
dopamine and, 520
neuroanatomical relationship, 589
false neurotransmitter hypothesis, 39
feedback control, 575function
affective and personality disorders, 511
other psychiatric disorders, 516glucoregulation, 571
innervation, nigrostriatal and mesolimbic pathways, 590
mechanism of action of antipsychotics, 588-mediated behaviors, antipsychotic drugs, 597
mesolimbic dopaniine pathways, 597
neuroleptic-induced catalepsy, 595
neuron, extracellular action potential (fig.), 564
neuropsychiatric disorders and, 507
neurotransmitter interaction, 516
other neurotransmitter receptors and, brain development, develop-
mental pharmacology, 553
overview of neuropsychiatric disorders, 510pharmacological implications, 521
physiological regulation, 569
postsynaptic receptor responsiveness, 515
precursors, neuroendocrine responses, 512
regulation of dopaminergic function, 595
role in psychiatric disorders, 509schizophrenia, 519-selective arylpiperazines, effects in humans, 527
uptake in platelets, 512Serotonin receptor agonists, neuroendocrine responses, 513Sertindole, cortical 5-HT2 and striated pK1 values (table), 593Setoperone, pK1 values (table), 592Sexual function, m-chlorophenylpiperazine, 538
Shunt, portal-systemic, reduction, hepatic encephalopathy, 54
Siever, Larry J., Ren#{233}S. Kahn, Brian A. Lawlor, Robert L. Trestman,
Timothy L. Lawrence, and Emil F. Coccaro. Critical issues in
defining the role of serotonin in psychiatric disorders, 509Skolnick, P. See Basile et al., 27Sleep
m-chlorophenylpiperazine, 538
REM, wakefulness transition, NCS 5-HT neuron (fig.), 566-wake-arousal continuum, 5-HT neurons (fig.), 566-wake-arousal cycle, 564
INDEX 615
excretion
Zacopride, clinical status (table), 583
Zotepine, pK1 values (table), 592
-wake cycle, DRN 5-HT neuron (fig.), 565
SM-9018, cortical 5-HT, and striated pK1 values (table), 593
Sodium, -hydrogen exchange, 487
transduction, a2-adrenoceptors and platelets (fig.), 488Sodium channels, voltage-sensitive, 323Sodium chloride, calcium and, intracellular accumulation, neurotoxic-
ity, 181Stadel, Jeffrey M. See Ruffolo et al., 475
Stressalprazolam and, corticotropin-releasing factor concentrations (fig.),
455brain 5-HT, 568
corticotropin-releasing factor neurons, 453
drug and behavioral effects, cerebellar cGMP, 3
secondary effects, 453
Suicide, controls and, composite Scatchard analysis, frontal cortical
sample (fig.), 460Sulfliydryl, replenishment, tolerance, organic nitrates, 402
Sumatriptanbiochemical and neurochemical effects, 581
clinical efficacy (table), 580clinical studies, 579
DHE and, neurotransmitter receptor (table), 581
history of (table), 579pharmacology of, 580side effect profile (table), 580
Synapsins
regulation of neurotransmitter release, 314
variants and alcoholism, 329
Tachycardia
atenolol and propranolol (fig.), 212salbutamol-induced, practolol or propranolol (fig.), 213
Tau factor
microtubule function, 332phosphorylation, neurofibrillary tangles, 332
Temperature
brain, DRN 5-HT neuron (fig.), 572
m-chlorophenylpiperazine, 534physiological effects, serotomn receptors, 543serotonin-selective arylpiperazines, 527
Tenilapine, pK1 values (table), 592
1,2,3,4-Tetranitratobutan, concentration-effect curve (fig.), 355
Thermoregulation, brain 5-HT, 570
Thioridazine, pED�,o (table), 594
Threitol tetranitrate, concentration-effect curve (fig.), 355
Threonine, -specific protein phosphatases, 312
brain (table),312
Thrombin, blood platelet receptors, 271
Thromboxane, prostaglandins and, 262
Thromboxane A,, Na�/W exchange, alpha adrenoceptors, platelets
(fig.), 488
Thyrotropin-releasing hormone, analogues, 18Tiospirone
pED�o (table), 594pK1 values (table), 592
Torfg#{226}rd,Kristina. See Ahlner et al., 351Trestman, RObert L. See Siever et a!., 509TRH peptides, cerebellar cGMP (table), 9Trinitro toluene, chemical structure of organic nitrate esters (fig.), 353
Tryptophan, plasma, 511
Tubulin, phosphorylation by cAMP-dependent protein kinase, 332
Tyrosine, -specific protein phosphatases, 313
Tyrosine hydroxylase, regulation of neurotransrnitter synthesis, 314
Urine
osmolality, pitressin (fig.), 89
V, antagonist (fig.), 88
vasopressin antagonists (fig.), 87
Vasculature, nitric oxide, 110, 129
Vasodilationinduced by nitrate esters, 354
nitrate esters, 356
Vasodilators, other antianginal drugs and, drug interactions, nitrates,
407
Vasopressin
antagonists
antidiuretic responses (table), 77
antidiuretic responses, 76
bioassay, definition of antagonist potency, 75
central and peripheral circulation, 78
change in urine excretion (fig.), 87
chemical structure and biological activity, 75
chemical structure of d(CH,),Tyr(Me)AVP (fig.), 77
chemical structure of V, antagonists (fig.), 77
elevated plasma arginine-vasopressin levels, 96
pharmacology and clinical perspectives, 73
physiological and pathophysiological roles, 78
potency, 76
pressor responses, 76
release, adrenocorticotrophic hormone, 90
serum osmolality, water content of brain (table), 90
serum sodium level, pitressin (fig.), 89
sodium excretion (fig.), 89
synthesis, 75
therapeutic effects, 97
treatment, clinical significance, 95
urine excretion and osmolality, pitressin (fig.), 89
urine excretion (fig.), 88
V2 and V, antagonists with opening rings (fig.), 79
vasopressor responses (table), 77
water metabolism, 86
binding studies and receptor isolation, 261
structure-activity relationships, 261
Visual-evoked response
abnormalities (fig.), 43
GABA/benzodiazepine receptor complex, 42
Walaas, Sven Ivar and Paul Greengard. Protein phosphorylation and
Water
neuronal function, 299
content of brain, serum osmolality, vasopressin antagonist (table),
90
metabolism, role, V2 antagonists, 86
Whit.aker-Azmitia, Patricia M. Role of serotonin and other neurotrans-
mitter receptors in brain development: Basis for developmental
pharmacology, 553
Wilker, Jeffrey C. and Wilmot, Carole A. Serotonin and neuropsychi-
atric disorders, 507
Wilmot, Carole A. See Wilker et a!., 507
Wood, Paul L. Pharmacology ofthe second messenger, cyclic guanosine
3’,5’-monophosphate, in the cerebellum, 1
Xamoterol, beta adrenoceptors, 214
Yohimbine, binding, competition by agonists and antagonists (table),
498