This document provides an overview of central nervous system (CNS) pharmacology. It discusses various ion channels and neurotransmitter receptors, including voltage-gated channels, ligand-gated channels, and metabotropic receptors. It also summarizes several neurotransmitters like acetylcholine, dopamine, GABA, glutamate, glycine, serotonin, norepinephrine, histamine, opioids, tachykinins, and endocannabinoids; describing their anatomy, receptor subtypes, agonists, antagonists, and mechanisms of action. Examples of ion channels and their toxin sources are also briefly outlined.

1. Introduction to
CNS pharmacology
By
Dr. Maria Qammar
(MBBS, M-Phil,
PhD scholar)

2. Ion channels & neurotransmitter
receptors
 Voltage gated channels ( Voltage
gated sodium channel of heart)
 Ligand gated channels (Ionotropic
receptors)
 Metabotropic receptors
 Membrane delimited
 Diffusible second messenger

3. Ion channels

4. Metabotropic receptors

5. Channel Types Mode of Toxin Action Source
Voltage-gated
Sodium channels
Tetrodotoxin (TTX) Blocks channel from outside Puffer fish
Batrachotoxin (BTX) Slows inactivation, shifts activation Colombian frog
Potassium channels
Apamin Blocks "small Ca-activated" K channel Honeybee
Charybdotoxin Blocks "big Ca-activated" K channel Scorpion
Calcium channels
Omega conotoxin (-CTX-GVIA) Blocks N-type channel Pacific cone snail
Agatoxin (-AGA-IVA) Blocks P-type channel Funnel web spider
Ligand-gated
Nicotinic ACh receptor
-Bungarotoxin Irreversible antagonist Marine snake
GABAA receptor
Picrotoxin Blocks channel South Pacific plant
Glycine receptor
Strychnine Competitive antagonist Indian plant
AMPA receptor
Philanthotoxin Blocks channel Wasp
Some Toxins Used to Characterize Ion Channels

6. The synapse & synaptic potentials
 Excitatory
 Excitatory post-synaptic potential (EPSP)
 Ionotropic receptor
 Inhibitory
 Inhibitory post-synaptic potential (IPSP)
 Presynaptic inhibition

7. Excitatory postsynaptic potentials (EPSP)

8. Interaction of excitatory and
inhibitory synapses

9. Site of
drug action

10. Central neurotransmitters
 Amino acids
 Neutral amino acids: glycine, GABA
 Acidic amino acids: glutamate
 Acetylcholine
 Monoamines
 Dopamine
 Norepinephrine
 5-hydroxytryptamine
 Peptides ( endorphin,
rnkephalin,somatostatin, neuropeptide Y)
 Nitric oxide
 endocananbiniods

11. Transmitter Anatomy Receptor Subtypes and
Preferred Agonists
Receptor Antagonists Mechanisms
Acetylcholine Cell bodies at all levels;
long and short connections
Muscarinic (M1): muscarine Pirenzepine, atropine Excitatory: in K+
conductance; IP3, DAG
Muscarinic (M2):
muscarine, bethanechol
Atropine, methoctramine Inhibitory: K+ conductance;
cAMP
Motoneuron-Renshaw cell
synapse
Nicotinic: nicotine Dihydro--erythroidine, -
bungarotoxin
Excitatory: cation
conductance
Dopamine Cell bodies at all levels;
short, medium, and long
connections
D1 Phenothiazines Inhibitory (?): cAMP
D2: bromocriptine Phenothiazines,
butyrophenones
Inhibitory (presynaptic):
Ca2+; Inhibitory
(postsynaptic): in K+
conductance, cAMP
GABA Supraspinal and spinal
interneurons involved in
pre- and postsynaptic
inhibition
GABAA: muscimol Bicuculline, picrotoxin Inhibitory: Cl–conductance
GABAB: baclofen 2-OH saclofen Inhibitory (presynaptic):
Ca2+ conductance;
Inhibitory (postsynaptic): K+
conductance
Summary of Neurotransmitter Pharmacology in
the Central Nervous System

12. Summary of Neurotransmitter Pharmacology in
the Central Nervous System
Transmitter Anatomy Receptor Subtypes and
Preferred Agonists
Receptor Antagonists Mechanisms
Glutamate Relay neurons at all levels
and some interneurons
N-Methyl-D-aspartate
(NMDA): NMDA
2-Amino-5-
phosphonovalerate,
dizocilpine
Excitatory: cation
conductance, particularly
Ca2+
AMPA: AMPA CNQX Excitatory: cation
conductance
Kainate: kainic acid,
domoic acid
Metabotropic: ACPD,
quisqualate
MCPG Inhibitory (presynaptic):
Ca2+ conductance cAMP;
Excitatory: K+
conductance, IP3, DAG
Glycine Spinal interneurons and
some brain stem
interneurons
Taurine, -alanine Strychnine Inhibitory: Cl–
conductance
5-Hydroxytryptamine
(serotonin)
Cell bodies in midbrain
and pons project to all
levels
5-HT1A: LSD Metergoline, spiperone Inhibitory: K+
conductance, cAMP
5-HT2A: LSD Ketanserin Excitatory: K+
conductance, IP3, DAG
5-HT3: 2-methyl-5-HT Ondansetron Excitatory: cation
conductance
5-HT4 Excitatory: K+
conductance

13. Summary of Neurotransmitter Pharmacology in
the Central Nervous System
Transmitter Anatomy Receptor Subtypes and
Preferred Agonists
Receptor Antagonists Mechanisms
Norepinephrine Cell bodies in pons and
brain stem project to all
levels
1: phenylephrine Prazosin Excitatory: K+
conductance, IP3, DAG
2: clonidine Yohimbine Inhibitory (presynaptic):
Ca2+ conductance;
Inhibitory: K+
conductance, cAMP
1: isoproterenol,
dobutamine
Atenolol, practolol Excitatory: K+
conductance, cAMP
2: albuterol Butoxamine Inhibitory: may involve in
electrogenic sodium
pump; cAMP
Histamine Cells in ventral posterior
hypothalamus
H1: 2(m-fluorophenyl)-
histamine
Mepyramine Excitatory: K+
conductance, IP3, DAG
H2: dimaprit Ranitidine Excitatory: K+
conductance, cAMP
H3: R--methyl-histamine Thioperamide Inhibitory autoreceptors

14. Summary of Neurotransmitter Pharmacology in
the Central Nervous System
Transmitter Anatomy Receptor Subtypes
and Preferred Agonists
Receptor Antagonists Mechanisms
Opioid peptides Cell bodies at all
levels; long and short
connections
Mu: bendorphin Naloxone Inhibitory
(presynaptic): Ca2+
conductance, cAMP
Delta: enkephalin Naloxone Inhibitory
(postsynaptic): K+
conductance, cAMP
Kappa: dynorphin Naloxone
Tachykinins Primary sensory
neurons, cell bodies at
all levels; long and
short connections
NK1: Substance P
methylester,
aprepitant
Aprepitant Excitatory: K+
conductance, IP3, DAG
NK2
NK3
Endocannabinoids Widely distributed CB1: Anandamide, 2-
arachidonyglycerol
Rimonabant Inhibitory
(presynaptic): Ca2+
conductance, cAMP

15. Schematic diagram of a glutamate synapse