INTRODUCTION TO CNS

PHARMACOLOGY

TARGETS OF CNS DRUG ACTION• Most drugs that act on the CNS appear by

changing ion flow through transmembrane channels of nerve cells.

• Types of ion channels :– Voltage-gated

respons to changes in membrane potential. Concentrated on the axon of nerve cells, cell bodies and

dendrites– Ligand-gated

respons to chemical neurotransmitter that bind to reseptor.

• Role of ion current carried by the channel :– EPSPs or excitatory postsinaptic potentials,

are generated by the opening of sodium or calcium channels.

– IPSPs or inhibitory postsinaptic potentials, are generated by the opening of pottasium or chloride channels.

• Role of CNS organization :– Hierarchial system

are delimited in their anatomic distribution and generally contain large

myelinated. It controls major sensory and motor function. The major EPSP is aspartat and glutamate, and the IPSP is GABA or glycine as transmitters.

– Diffuse systems

are broadly distributed, single cell (axon) sending processes to many different

areas. The transmitters in diffuse system are norepinephrine, dopamin, serotonin or peptides that action on metabotropic receptors.

• Criteria for neurotransmitter :–Must present in high concentration in synaptic

area.–Must be released by stimulation via calcium-

dependent mechanism–Must produce the same sort of postsynaptic

response

ACETYLCHOLINE • Brain neurons have reseptor for ACh and most

CNS response to ACh. • Drugs affecting the activity of cholinergic

system in the brain include the acethylcholinesterase inhibitors used in Alzheimer’s disease (eg.tacrine) and muscarinic blocking agents used in parkinsonism (eg.benztropine).

DOPAMINE• Dopamine reseptor the major in basal ganglia

neurons and widely distributed at the supraspinal level.

• Drugs affecting the activity of dopaminergic include antipsikotics (eg.chlorpromazine), CNS stimulants (eg.amphetamine) and antiparkinsonsm drugs (eg.levodopa)

NOREPINEPHRINE• Are mainly located in the brain stem and the

lateral tegmental area of the pons.• Excitatory effects are caused by activation of

alpha1 and beta1 reseptors.• Inhibitory effects are caused by activation of

alpha2 and beta2 reseptors.

SEROTONIN• Serotonin pathways from cell bodies or midline

regions of the pons and upper brain stem.• Used in the treatment of major depressive

disorder (eg.tricyclic antidepressant, selective serotonin reuptake inhibitors)

GLUTAMIC ACID• Most neurons in the brain are excited by

glutamic acid.• Subtypes of glutamate reseptors include the

NMDA reseptor which is blocked by phencyclidine and ketamin.

GABA AND GLYCINE• Is the primary neurotransmitter IPSP in neurons

in the brain.• Drugs that influence GABAergic system include

sedative-hypnotic (eg.barbiturates, benzodiazepines), anticonvulsants (eg.gabapentin).

• Glycine reseptors more numerous in the cord, are blocked by strychnine (a spinal convulsant)

PEPTIDE TRANSMITTER• Identified in the CNS. Important therapeutic

action for opioid analgesics (eg.morphine)

THANK YOU