INTRODUÇÃO AO SISTEMA NERVOSO CENTRAL
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Transcript of INTRODUÇÃO AO SISTEMA NERVOSO CENTRAL
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INTRODUÇÃO AO SISTEMA NERVOSO
CENTRAL
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Sistema
Nervoso
Central
SistemaNervosoPeriféric
o
Nervos
Encéfalo
Cérebro
Cerebelo
TroncoEncefálico
Mesencéfalo
Ponte
Bulbo
Medulaespinhal
GângliosTerminações nervosas
Espinhais
Cranianos
SN
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Anatomia macroscópica
Basal ganglia
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terminal axonfibers
dendrites
axon
cell body
1-1 Stahl S M, Essential Psychopharmacology (2000)
ANATOMIA MICROSCÓPICA - NEURÔNIO
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1-2 Stahl S M, Essential Psychopharmacology (2000)
dendritic spines
cell body
dendrites
synaptic vesicles
spine
dendrite
postsynaptic density
axon
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presynapticneuron
postsynapticneuron
mitochondrion
vesicles
synaptic cleft1-3 Stahl S M, Essential
Psychopharmacology (2000)
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neurotransmitter(first messenger)
bound neurotransmitterreceptor
second messenger
cellular actions1-10 Stahl S M, Essential
Psychopharmacology (2000)
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Regulação dos genes por NT ou psicofármacos
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2--35 Stahl S M, Essential Psychopharmacology (2000)
first messenger neurotransmitter
receptor second messenger
neuronal membrane
inactive protein kinase
activation active protein kinase
inactive transcription
factor
activated “early” transcription factor
mRNA
FOS
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2-42 Stahl S M, Essential Psychopharmacology (2000)
mRNA
mRNA
mRNA
Late gene products
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Regulação do número de receptores:
“Down-regulation” e “Up-regulation”
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2-43 Stahl S M, Essential Psychopharmacology (2000)
DOWN REGULATIONDOWN REGULATION
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2-44 Stahl S M, Essential Psychopharmacology (2000)
UP REGULATIONUP REGULATION
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2-45 Stahl S M, Essential Psychopharmacology (2000)
Down Regulation
Up
Reg
ula
tio
n
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TIPOS DE RECEPTORES MAIS TIPOS DE RECEPTORES MAIS FREQUENTES EM SNCFREQUENTES EM SNC
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side view of receptor with seven transmembrane regions
extracellular
intracellular
membrane transmembrane
2-2 Stahl S M, Essential Psychopharmacology (2000)
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5 copies of the ligand gated ion channels receptors make a functioning channel
2-6 Stahl S M, Essential Psychopharmacology (2000)
channel
=
Four transmembrane regions
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2-7 Stahl S M, Essential Psychopharmacology (2000)
12 transmembrane regions
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7 transmembrane region G protein
linked
4 transmembrane ligand gated ion
channel
12 transmembrane region transporter
2-13 Stahl S M, Essential Psychopharmacology (2000)
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INTERAÇÃO FÁRMACO-RECEPTOR
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Haloperidol
X
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GABA site
BZ site
picrotoxin site
alcohol site
barbiturate site
8-20 Stahl S M, Essential Psychopharmacology (2000)
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2-20 2-21 2-22
Stahl S M, Essential Psychopharmacology (2000)
= fluoxetine (Prozac)
= serotonin
= sodium
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2-24 Stahl S M, Essential Psychopharmacology (2000)
= fluoxetine
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NEUROTRANSMISSORES
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Critérios para identificação dos NT
• Síntese no local de liberação
• Armazenagem
• Presença no espaço sináptico e ação pós-sináptica
• Ativação de Receptores
• Presença de enzimas inativadoras
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AMINOÁCIDOS
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GLUTAMATE
GABA IS PRODUCED
Glu-AD
GABA
GABA8-16 Stahl S M, Essential
Psychopharmacology (2000)
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GABA IS DESTROYED
GABA T destroys
GABA
GABA transporter
8-17 Stahl S M, Essential Psychopharmacology (2000)
Metabólito = semi-aldeído succínico
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GABA RECEPTORS
GABA transporter
GABA A
receptor
GABA B receptor
8-18 Stahl S M, Essential Psychopharmacology (2000)
Baclofen
muscimol
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GABA site
BZ site
picrotoxin site
alcohol site
barbiturate site
8-20 Stahl S M, Essential Psychopharmacology (2000)
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GABABZ
8-21 Stahl S M, Essential Psychopharmacology (2000)
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GABABZ
BZ
GABA
8-23 Stahl S M, Essential Psychopharmacology (2000)
HIPERPOLARIZAÇÃO
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GLU (Glutamate)
Glutamine
GLUTAMATE IS PRODUCED
GlutaminaseGlutamate
Glutamate
Glutamine synthase
Glutamine
Glial cell
10-21 Stahl S M, Essential Psychopharmacology (2000)
Transportadores (ASCT2, GlnT, SN1)
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GLUTAMATE IS REMOVED
10-22 Stahl S M, Essential Psychopharmacology (2000)
Glial cell
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GLUTAMATE RECEPTORS
NMDA receptor
AMPA receptor
kainate receptor
metabotropic receptor
10-23 Stahl S M, Essential Psychopharmacology (2000)
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GLUTAMATE RECEPTORS
ReceptorNMDA
ReceptorAMPA
Cainato ReceptorMetabotrópico= 8
LTP
PCP
Calcium channel
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glycine site
zinc site
polyamine site
Mg site (in the ion channel)
PCP site (in the ion channel)
10-24 Stahl S M, Essential Psychopharmacology (2000)
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ACETILCOLINA
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Glucose
ACETYLCHOLINE IS PRODUCED
CAT
Choline
ACh
ACh12-8 Stahl S M, Essential
Psychopharmacology (2000)
AcCoA
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AChE
ACETYLCHOLINE IS DESTROYED
AChE
12-9 Stahl S M, Essential Psychopharmacology (2000)
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ACETYLCHOLINE RECEPTORS
presynaptic M2 receptor
M1 receptor
M2 MXN
12-10 Stahl S M, Essential Psychopharmacology (2000)
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hippocampus
frontal
neocortex
amygdala
Nucleus basalis of Meynert
Acetylcholine Pathways
Ch1=medial septal nucleusCh2=vertical nucleus of the diagonal bandCh3=horizontal nucleus of the diagonal bandCh4=n basalis de Meynert
Basal forebrain
Ch1Ch2
Ch4
Ch3
(Mediate memory, learning, problem solving, judgement)
Loss in NB-Ch4 Alzheimer’s disease
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striatum
lateral tegmental area
12-12 Stahl S M, Essential Psychopharmacology (2000)
Upper pons/mesencephalon
Medullary Ach neurons
thalamus
Interneurons involved in regulating motor movements
Arousal, attention, sleep
Parkinson
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CATECOLAMINAS
E INDOLAMINAS
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tyrosine transporter
TOH
TYR
DOPA
DDC
DA (Dopamine)
DOPAMINE IS PRODUCED
5--31 Stahl S M, Essential Psychopharmacology (2000)
dihydroxyphenylalanine)
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COMTdopamine transporter
MAO
DOPAMINE IS DESTROYED
5--32 Stahl S M, Essential Psychopharmacology (2000)
(DOPAC - Ácido diidroxifenilacético)
Ácido homovanílico
DOPAC,HVA
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DOPAMINE RECEPTORS
presynaptic autorecptor
D1 D2 D3 D4 D5
dopamine transporter
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hypothalamus
d
c
Nucleus accumbens
Tegmentum
bSubstantia nigra
Basal Ganglia
a
DOPAMINE PATHWAYS
10-7 Stahl S M, Essential Psychopharmacology (2000)
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mesolimbic pathway
Part of limbic system – involved in pleasurable sensations, motivation, delusions and hallucinations of psychosis
Midbrain VTA
Nucleus accumbens
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mesolimbic overactivity = positive symptoms of psychosis
10-9 Stahl S M, Essential Psychopharmacology (2000)
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meso-cortical pathway
VTA
Limbic Cortex
Memory, attention, problem solving
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nigrostriatal pathway
SN
Basal ganglia
Part of the extrapyramidal nervous systemControls movements
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EPSs
Stahl S M, Essential Psychopharmacology (2000)
Nigrostriatal pathway
When DA is deficient, it can cause parkinsonism with tremor, rigidity.When DA is in excess, it can cause hyperkinetic movements such as tics and dyskinesias.
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tubero infundibular pathway
10-13 Stahl S M, Essential Psychopharmacology (2000)
hypothalamus
Pituitary gland
Controls prolactin secretion
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Prolactin levels rise
11-6 Stahl S M, Essential Psychopharmacology (2000)
Tuberoinfundibular pathway
D2 receptors are blocked
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NE (norepinephrine)
tyrosine transporter
TYR
TOH
DOPA
DDC DA
DBH
NOREPINEPHRINE IS PRODUCED
5-17 Stahl S M, Essential Psychopharmacology (2000)
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NOREPINEPHRINE IS DESTROYED
COMT destroys NEnorepinephrine
transporter
MAO
5-18 Stahl S M, Essential Psychopharmacology (2000)
MHPG3-metoxi-4-hidroxifenilglicol
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NOREPINEPHRINE RECEPTORS
presynaptic alpha 2 autoreceptor
postsynaptic alpha 2
receptorpostsynaptic beta 1 receptor
alpha 1 receptor
5-19 Stahl S M, Essential Psychopharmacology (2000)
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Norepinephrine Pathways
Locus Coeruleus
5-23 Stahl S M, Essential Psychopharmacology (2000)
PFC
PFC
Limbiccortex
Cerebellum
Brainstem
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beta 1 receptor
5-24 Stahl S M, Essential Psychopharmacology (2000)
Depression/AnxietyFrontal 1
Mood
Overactivity at the postsynaptic beta receptors increases anxietyNE deficiency = depressed mood
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alpha 2 receptor
Frontal 2 Attention
5-25 Stahl S M, Essential Psychopharmacology (2000)
Alpha 2 receptor = regulates attention, concentration, working memory, speed of informationNE deficiency = impaired attention, problems concentrating, deficiencies in working memory
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5-26 Stahl S M, Essential Psychopharmacology (2000)
Limbic
EmotionsAgitationEnergy Level
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5-27 Stahl S M, Essential Psychopharmacology (2000)
Cerebellum Tremor
Motor movements
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5HT (Serotonin)
SEROTONIN IS PRODUCEDtryptophan transporter
TRY-OH
5HTP
AAADC
Tryptophan
5--34 Stahl S M, Essential Psychopharmacology (2000)
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serotonin transporter
MAO
SEROTONIN IS DESTROYED
5--35 Stahl S M, Essential Psychopharmacology (2000)
5-HIAAÁc. 5-hidroxi-indol-acético
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SEROTONIN RECEPTORS
alpha 2 hetero receptor
5HT1D autoreceptor
5HT1A
serotonin transporter
5HT2A5HT2C
5HT3 5HT45HTX
5HTY
5HTZ
5--36 Stahl S M, Essential Psychopharmacology (2000)
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Serotonin Pathways
Raphe Nucleus
5--51 Stahl S M, Essential Psychopharmacology (2000)
PFC
Basalganglia
Limbic
Hypothalamus
Sleep center
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5--52 Stahl S M, Essential Psychopharmacology (2000)
Frontal Cortex Mood
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5--53 Stahl S M, Essential Psychopharmacology (2000)
Basal Ganglia OCDAkathisia/Agitation
5-HT control movements as well as obsessions and compulsions
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5--54 Stahl S M, Essential Psychopharmacology (2000)
Limbic Anxiety/ Panic
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5--55 Stahl S M, Essential Psychopharmacology (2000)
Hypothalamus Appetite/bulimia
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5--56 Stahl S M, Essential Psychopharmacology (2000)
Brainstem Sleep Centers Insomnia
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5--57 Stahl S M, Essential Psychopharmacology (2000)
Spinal Cord Sexual Dysfunction
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5--58 Stahl S M, Essential Psychopharmacology (2000)
Brainstem Vomiting Center
Nausea and vomiting
5-HT3
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Ações de Fármacos no SNC
• Ação específica vs inespecífica
• Ações gerais ou inespecíficas:– Depressores gerais do SNC – anestésicos gerais
inalatórios– Estimulantes gerais do SNC – PTZ
• Ações específicas: atuam seletivamente no SNC, deprimindo ou estimulando as funções do SNC (anticonvulsivantes, antidepressivos, sedativos, hipnóticos, psicoestimulantes…)
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Alvos das ações de fármacosAlvos das ações de fármacos
N
PRECURSOR
1
N
N
N
2
3
4
N
4
N
5
6
7
1 – Síntese2 – Armazenamento3 – Liberação4 – Interação com receptores5 – Recaptação6 – Catabolismo extra-neuronal7 – Catabolismo intra-neuronal
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DOPAMINA
phenylalaninePA-OHase
Tir-OHase
Estimula adenilato-ciclase
Inibe a adenilato-ciclase
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Classificação dos fármacos de ação Classificação dos fármacos de ação centralcentral
• Psicolépticos: a atividade psíquica normal ou alterada. – Antipsicóticos (neurolépticos). Ex: haloperidol– Ansiolíticos. Ex: diazepam, CDZ– Hipnóticos. Ex: flurazepam, barbitúricos
• Psicoanalépticos: ↑ a atividade psíquica normal ou alterada.– Antidepressivos. Ex: imipramina, tranilcipromina– Psicoestimulantes. Ex: anfetamina
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Psicodislépticos: promovem alterações de sensopercepção (alucinações, delírios, euforia)
- Psicotogênicos ou alucinógenos. Ex: LSD, mescalina- Euforizantes e desinibidores. Ex: cocaína, etanol, heroína
Normalizadores psíquicos: corrigem estados psíquicos anormais
Eutímicos. Ex: sais de lítioEnergizantes ou nootrópicos. Ex: piracetam, piritinol