3 Clinical psychopharmacology3.3 Pharmacodynamics

3.3.1.2.2 Ionotropic receptors

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Written by Resident Doctor Committee · Published

Ionotropic and metabotropic receptors

  • Ionotropic receptors are ligand-gated ion channels in which the receptor protein itself forms the pore, so transmitter binding opens the channel within milliseconds.

  • Metabotropic receptors are G protein-coupled and act through separate channels or intracellular pathways.

Family

Structure

Members

Cys-loop

Five subunits around the pore

GABA-A, glycine, nicotinic acetylcholine, 5-HT3

Ionotropic glutamate

Four subunits

AMPA, kainate, NMDA

GABA-A (gamma-aminobutyric acid type A) and glycine receptors pass chloride and are usually inhibitory. The others pass cations and usually depolarise.

Drugs of misuse

Drug

Receptor

Receptor type

Benzodiazepines

GABA-A

Ionotropic

Ketamine

NMDA

Ionotropic

GHB (gamma-hydroxybutyrate)

GABA-B

Metabotropic

LSD (lysergic acid diethylamide)

5-HT2A

Metabotropic

GABA-A receptors and benzodiazepines

  • Benzodiazepines act through the GABA-A receptor complex, a ligand-gated chloride channel, and not through the metabotropic GABA-B receptor.

  • GABA-A forms its own chloride pore, so activation raises membrane chloride permeability.

  • Benzodiazepines are positive allosteric modulators: they bind the alpha-gamma-2 interface, separate from the GABA site, and increase the effect of GABA already bound.

  • They make the channel open more often but cannot open it without GABA, so benzodiazepine overdose alone is rarely fatal.

  • Barbiturates prolong opening and open the channel directly at high concentrations, so their overdose can be fatal.

The benzodiazepine (BZD) site sits at the alpha-gamma2 interface, separate from the two GABA sites, on a five-subunit receptor that forms its own chloride pore. Д.Ильин : vectorization, CC0, via Wikimedia Commons

5-HT3 receptors

  • 5-HT3 is the only ionotropic serotonin (5-hydroxytryptamine) receptor, and its activation on vagal afferents and in the area postrema contributes to nausea.

  • Mirtazapine affects nausea through its 5-HT3 antagonism, not through its alpha-2, 5-HT2A, 5-HT2C or indirect 5-HT1A actions.

  • Ondansetron also blocks 5-HT3.

Revision material for the MRCPsych examinations. Not clinical guidance, and not for use in patient care.