Ionotropic serotonin receptors

There are two main families of ligand-gated ion channel proteins that act as ionotropic receptors. One family includes the nicotinic acetylcholine receptor, the GABA-A receptor, the glycine receptor, and a class of serotonin receptor. The other family comprises various types of ionotropic glutamate receptors. Since these various ligand gated ion channels are activated by neurotransmitters, the medicinal chemistry of these proteins is presented in detail in chapter 4. 

Members of all serotonin receptor families except the 5-HTg receptor (Hamon et al. 1999 Marcos et al. 2006) occur presynaptically. Presynaptic 5-HT3 receptors are discussed in this Handbook in the chapter on ionotropic receptors by Dorostkar and Boehm. 

Table 3.3 Ionotropic glutamate, glycine and serotonin receptors...

HT1A-R, metabotropic 5-hydroxy-tryptamine (serotonin) receptor 5-HT1-R, metabotropic 5-hydroxy-tryptamine (serotonin) receptor 5HT2-R, metabotropic 5-hydroxy-tryptamine (serotonin) receptor 5HT3-R, ionotropic 5-hydroxytryptamine receptor... 

Mode of action. The precise mode of action of carbamazepine has not been fully established. It has been shown to stabilize both pre- and postsynaptic neurons by blocking the use and frequency-dependent sodium channels. While this is probably its main action, the blockade of the glutamate NMDA ionotropic receptors also leads to a reduction in the influx of sodium and calcium ions into the neuron. The net effect of these changes is a reduction in the sustained high-frequency repetitive firing of the action potentials which characterize epileptic activity. There is also evidence that carbamazepine blocks purine, noradrenaline, serotonin and muscarinic acetylcholine receptors which probably accounts for the use of carbamazepine as a mood stabilizing agent. 

The neurotransmitter, glutamate, is a major excitatory neurotransmitter. Glutamate receptors are called ionotropic receptors. The effect of glutamate is to cause charged ions such as Na and Ca " to pass through a channel in the centre of the receptor complex, which results in a depolarization of the plasma membrane and the generation of an electrical current that is propagated down the dendrites and axons of the neuron. Kandel found that cyclic AMP increased when these effects were retained in the neurons, to provide a chemical foundation of short-term memory. Cyclic AMP activates an enzyme, protein kinase, which acts like a neuronal switch. Serotonin increases this reaction. 

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