cgp 36216 hydrochloride is a potent and selective antagonist of gabab receptors with ic50 value of 43 μm.gabab receptors (gababr) are metabotropic transmembrane receptors for gamma-aminobutyric acid (gaba) and are linked through g-proteins to potassium channels. expression of gabab receptors are found in the central as well as in the autonomic division of the peripheral nervous system. gabab receptors play a key role in regulating membrane excitability and synaptic transmission in the brain.in rat neocortical preparations maintained in mg2+-free krebs medium, cgp 36216 acts as antagonism of baclofen-induced suppression of spontaneous discharges in a concentration-dependent manner. however, cgp 36216, up to 1 mm, was ineffective in antagonising baclofen-induced hyperpolarisations, mediated through gamma-aminobutyric acid (b) gabab postsynaptic receptors 1.in electrically stimulated brain slices preloaded with [3h] gaba, cgp 36216 increased the release of [3h] gaba, that was reversed by baclofen. while cgp 36216 is ineffective at gabab postsynaptic receptors, it is appreciably more active at presynaptic receptors1.
1. ong j, bexis s, marino v, et al. cgp 36216 is a selective antagonist at gaba(b) presynaptic receptors in rat brain. european journal of pharmacology. 2001;415(2-3):191-195.
