neurons & neural transmission neurochemical mechanisms of drug action

NEURONSNEURONS&&

NEURAL TRANSMISSIONNEURAL TRANSMISSION

NEUROCHEMICAL MECHANISMS OF NEUROCHEMICAL MECHANISMS OF DRUG ACTIONDRUG ACTION

Nervous System DivisionsNervous System Divisions CNS (central nervous CNS (central nervous

system)system) Brain, Spinal Cord Brain, Spinal Cord 12 pairs of cranial nerves 12 pairs of cranial nerves

(originate from cranium)(originate from cranium)

PNS (peripheral nervous PNS (peripheral nervous system)system) Somatic nervous systemSomatic nervous system

• 31 pairs of spinal nerves31 pairs of spinal nerves Autonomic nervous systemAutonomic nervous system

CNS ORGANIZATIONCNS ORGANIZATION

Autonomic Nervous SystemAutonomic Nervous System

NEURONSNEURONS

NEURON MEMBRANENEURON MEMBRANE

Membrane StructureMembrane Structure Semipermeable lipid Semipermeable lipid

bilayerbilayer ProteinsProteins

• Ion channelsIon channels• Transport pumpsTransport pumps• ReceptorsReceptors

MEMBRANE POTENTIALMEMBRANE POTENTIAL

ACTION POTENTIALACTION POTENTIAL

ACTION POTENTIALACTION POTENTIAL

CONDUCTION OF A.P.CONDUCTION OF A.P.

NEURONAL COMMUNICATIONNEURONAL COMMUNICATION

POSTSYNAPTIC POSTSYNAPTIC POTENTIALSPOTENTIALS Excitatory PSPExcitatory PSP Inhibitory PSPInhibitory PSP

NEUROCHEMICAL SYNAPSENEUROCHEMICAL SYNAPSE

Presynaptic Presynaptic MembraneMembrane

Postsynaptic Postsynaptic MembraneMembrane

Synaptic VesiclesSynaptic Vesicles Synaptic CleftSynaptic Cleft Receptor SitesReceptor Sites

SYNAPTIC TRANSMISSIONSYNAPTIC TRANSMISSION SynthesisSynthesis StorageStorage Neurotransmitter Neurotransmitter

ReleaseRelease Receptor ActivationReceptor Activation Neurotransmitter Neurotransmitter

DeactivationDeactivation Enzymatic Deactivation Enzymatic Deactivation

(Metabolism)(Metabolism) ReuptakeReuptake

SYNTHESISSYNTHESIS

NEUROTRANSMITTER FAMILIESNEUROTRANSMITTER FAMILIES AcetylcholineAcetylcholine MonoaminesMonoamines

NorepinephrineNorepinephrine DopamineDopamine SerotoninSerotonin

Amino Acid TransmittersAmino Acid Transmitters GlutamateGlutamate GABAGABA HistamineHistamine GlycineGlycine

NeuropeptidesNeuropeptides EnkephalinsEnkephalins EndorphinsEndorphins

Receptor Subtypes for Receptor Subtypes for NeurotransmittersNeurotransmitters

Acetylcholine: nicotinic, muscarinicAcetylcholine: nicotinic, muscarinic Dopamine: D1, D2, D3, D4, D5Dopamine: D1, D2, D3, D4, D5 Norepinephrine: alphaNorepinephrine: alpha11, alpha, alpha22, beta, beta11, beta, beta22

Serotonin: 5-HTSerotonin: 5-HT1a,1b,1c,1d1a,1b,1c,1d; 5-HT; 5-HT2a,2b,2c;2a,2b,2c;; 5-HT; 5-HT3…3…

GABA: GABAGABA: GABAAA, GABA, GABABB

Glutamate: NMDA, AMPA, mGluRGlutamate: NMDA, AMPA, mGluR Endorphins: mu, kappa, deltaEndorphins: mu, kappa, delta

NEUROCHEMICAL PATHWAYSNEUROCHEMICAL PATHWAYS

RECEPTOR ACTIVATIONRECEPTOR ACTIVATION Ligand-gated ion channelsLigand-gated ion channels Ionotropic ReceptorsIonotropic Receptors Metabotropic ReceptorsMetabotropic Receptors

G proteinsG proteins Second MessengersSecond Messengers

RECEPTOR ACTIVATIONRECEPTOR ACTIVATION

DRUG ACTIONS ON RECEPTOR DRUG ACTIONS ON RECEPTOR ACTIVATIONACTIVATION

AgonistsAgonists Competitive Competitive NoncompetitiveNoncompetitive

AntagonistsAntagonists CompetitiveCompetitive NoncompetitiveNoncompetitive

PRESYNAPTIC MECHANISMSPRESYNAPTIC MECHANISMS

POSTSYNAPTIC MECHANISMSPOSTSYNAPTIC MECHANISMS

Psychoactive Drug ClassesPsychoactive Drug Classes CNS stimulantsCNS stimulants

amphetamine, cocaine, caffeine, nicotineamphetamine, cocaine, caffeine, nicotine CNS depressantsCNS depressants

alcohol, benzodiazepines, barbiturates, GHB alcohol, benzodiazepines, barbiturates, GHB HallucinogensHallucinogens

LSD, PCP, mescaline, MDMA(?)LSD, PCP, mescaline, MDMA(?) Narcotics (Opioids)Narcotics (Opioids)

morphine, methadonemorphine, methadone AntipsychoticsAntipsychotics

chlorpromazine, haloperidol, clozapine, chlorpromazine, haloperidol, clozapine, risperidonerisperidone

AntidepressantsAntidepressants SSRIs (e.g., Prozac, Paxil), MAOIs, tricyclicsSSRIs (e.g., Prozac, Paxil), MAOIs, tricyclics

Pharmacology of Psychoactive DrugsPharmacology of Psychoactive Drugs

Drugs with cholinergic actionsDrugs with cholinergic actions curare (nicotinic antagonist)curare (nicotinic antagonist) atropine (muscarinic antagonist)atropine (muscarinic antagonist) nicotine (nicotinic mixed agonist/antagonist)nicotine (nicotinic mixed agonist/antagonist)

Nonselective monoamine agonists Nonselective monoamine agonists reserpinereserpine MAO inhibitors (e.g., deprenyl)MAO inhibitors (e.g., deprenyl) tricyclic antidepressants (e.g., imipramine)tricyclic antidepressants (e.g., imipramine) CNS stimulants (e.g., cocaine, amphetamine)CNS stimulants (e.g., cocaine, amphetamine)

Pharmacology of Psychoactive DrugsPharmacology of Psychoactive Drugs

Other dopaminergic drugsOther dopaminergic drugs antipsychotics (haloperidol, chlorpromazine)antipsychotics (haloperidol, chlorpromazine) antiparkinson agents (L-DOPA, bromocriptine)antiparkinson agents (L-DOPA, bromocriptine)

Serotonergic drugsSerotonergic drugs SSRIs -- (Prozac, Paxil)SSRIs -- (Prozac, Paxil) LSDLSD

GABAergic drugsGABAergic drugs benzodiazepines (Valium, Xanax)benzodiazepines (Valium, Xanax) alcoholalcohol bicuculline (convulsant)bicuculline (convulsant)

Pharmacology of Psychoactive Pharmacology of Psychoactive DrugsDrugs