Neurotransmitters, Neuromodulators, and their

receptors

The following slides provides a summary of the major classes of neurotransmitters and the names of the receptors that have been identified. The drugs listed in these slides are drugs that affect

neuronal transmission by attaching to the post and pre-synaptic receptors. Other drugs (not listed in these slides) affect neuronal

functioning by altering some other function of a neuron.

Neurotransmitters (NT) & Neuromodulators (NM)

1. Acetylcholine (NT)

2. Monoamines (NT; NM)

3. Amino Acids (NT; NM)

4. Peptides (NT; NM)

5. Lipid-like substances (NT)

6. Nucleosides (NM)

7. Soluble gases

A. Catecholamines

B. Indolamines

•Dopamine

•norepinephrne

•epineprine

•Serotonin

• Glutamate• GABA

• GlycineEndorphins, enkephalins

Anandamide, leptin

adenosine

Nitric Oxide, Carbon Monoxide(atypical)

Types of drugs base on their effects on receptors

Agonist - a drug that binds with and activates a postsynaptic receptor.

Antagonist - a drug that binds with a postsynaptic receptor and does not activate it; may block the natural transmitter from binding with the receptor

Different subtypes of Agonists and antagonists are described on the next slide

(also called Receptor Blocker)

(A better but never used term is indirect antagonist)

Receptor subtypes

Receptors belonging to one class of neurotransmitters (e.g. Dopamine) may respond differently to various drugs. When this is the case the receptors are divided into subclasses.

E.g. There are several Dopamine receptors, each responding to dopamine but differently to different drugs. These receptors are called D1, D2, D3, D4, and D5 receptors

1. Acetylcholine (cholinergic or acetylcholinergic neurons)

Competitive agonist & antagonists

Agonist AntagonistNicotinic Receptor Nicotine Curare

Muscarinic Receptor Muscarine Atropine

A. Catecholamines (primarily neuromodulators)

1. Dopamine (Dopaminergic neurons; produces EPSPs orIPSPS)

Agonist AntagonistD1 – D5Receptors

Apomorphine(note: this drug is an

antagonist ofautoreceptors, but because

neuronal activity isfacilitated it is classified

as an Da agonist)

Chlorpromazine(D2)

2. Norepinephrine (Noradrenergic neurons)Agonist Antagonist

1, 2; 1,2Receptors

Clonidine(2)

Yohimbine (2)

3. Epinephrine (Adrenergic neurons)

2. Monoamines

B. Indolamines

1. Serotonin (5-HT; Serotonergic neurons)

Agonist AntagonistA1, A2 Floxetine

(Prozac)PCPA

2. Monoamines

A. Glutamate (glutamatergic neurons)Principle Excitatory neurotransmitter in brain& spinal cord

Agonist commentsNMDA receptor

(ionotropic)NMDA 6 binding sites; controls

Na+ & Ca++; EtOH binding site?;PCP ("angel dust") is

antagonistAMPA receptor

(ionotropic)AMPA Most common; controls

Na+Kainate receptor

(ionotropic)Kainate acid controls Na+

metabotropicreceptor

--- May be 6 or more ofthese; some areautoreceptors

3. Amino Acids

B. GABA (GABA-secreting neurons)- Principle Inhibitory neurotransmitter in brain & spinalcord- Drugs at Sites 2-5 acts as noncompetitiveagonists/antagonists- B-CCM may be a natural transmitter for thebenzodiazepine site.

Agonist AntagonistsGABA A Site 1: GABAIonotropicControls Cl-channel

Site 2: Benzodiazepines(Valium; Librium, alcohol?) –AnxiolyticsSite 3: BarbituratesSite 4: steroids

Site 5: picrotoxin(inverse agonist)

GABA BMetabotropic Controls K+channel

Baclofen (opens K+channels)

3. Amino Acids cont.

C. Glycine

Inhibitory neurotransmitter in the spinal cord & lowerbrainstem

Agonist AntagonistsGlycine receptor strychnine none

3. Amino Acids cont.

- Chains of two or more amino acids- produced from larger polypeptide chains (precursor

molecules)- no reuptake or recycling of peptides- serve as neurotransmitters and neuromodulators

e.g., endogenous opioid peptides (endorphins,enkephalins)

Agonist AntagonistsMu opiate receptor Morphine, heroin,

Percodannaloxone

Delta opiate receptorKappa opiate receptor

4. Peptides

A. anandamideAgonist Antagonists

THC receptor THC ?

B. LeptinAgonist Antagonists

Leptin receptor ? ?

5. Lipid-like substances

e.g., adenosine- serves as a neuromodulator- released by adenosinergic neurons & glial cells- produces inhibitory effects by opening K+ channels

Agonist Antagonists3 types ofmetabotropic receptors

? Caffeine

6. Nucleosides (sugar molecule +purine or pyrimidine)

- produced in several regions of neurons includingdendrites

- released as soon as produced- dilates blood vessels in active brain areas and

causes penile erection- enters cells and activates second messenger cyclic

GMP

A. nitric oxide (NO)B. carbon monoxide (CO)

7. Soluble Gases