Question

For Barbiturates answer the following:

- Type of receptor it binds to. Ion channel recept or GPCRs, is it excitatory or inhibitory on postsynaptic cell.

- Identify the endogenous molecule that the drug is interacting with and how it changes its function.

-Discuss the changing synaptic transmission by drugs based on the neural circuits that are affected.

Answer 1

Barbiturates are class of drug which are potential allosteric modulators. It also can act as GABA receptor agonist which is the principal inhibitory neurotransmitter in CNS. The principle receptor for barbiturates are GABA receptors on which it binds at multiple homologous transmembrane pockets of subunit interface. It also effect the entire superfamily of ligand-gated ion channels and GABAA is just one among them. It also block ionotropic glutamate receptor subtypes. The CNS-depressant effects is well explained by the predominant effect of inhibitory GABAA receptors and inhibit excitatory AMPA receptors. Barbiturates inhibit the calcium dependent release of glutamate by affecting P/Q type voltage- dependent calcium channels. It also increases the duration of release of chloride ion channel. In addition it also interferes with the Cys-loop receptor superfamily of ion receptors such as neuronal nACh receptor channel, 5-HT receptor channel and glycine receptor channel.

Barbiturates may increase the probability of an action potential fails to invade every branch of the axonal arbour which could affect the synaptic drive to the postsynaptic neurons. This could be done by inhibiting calcium influx in presynaptic neuron contributes to its depressant effect on excitatory synaptic transmission in the CNS. It has been observed that at pentobarbitone concentration, the synaptic transmission shows significant depression. The significant reduction in the AP propogation is observed in procaine concentration.

The most important potential sites of action of barbiturates at central synapse