Partial GABA agonist

Fig. 3. Schematic illustration of synaptic contacts between central acetylcholine (ACh), glutamic acid (Glu) and y-aminobutyric acid (GABA) neurones and their receptors (for details see subsequent sections). The structures of the specific GABA agonists isoguvacine and (THIP) [72] and the low-efficacy partial GABA agonist 5-(4-piperidyl) isoxazol-3-ol (4-PIOL) [30] are indicated.

Fig. 8. Effects of the full GABA agonist muscimol, the efficacious partial GABAa agonist THIP, and the low-efficacy partial GABA agonist, 4-PIOL, on the binding of radioaetive diazepam at 0°C and in the absence of chloride ( ), or at 30°C in the presence ( ) or absence (o) of 150mM sodium chloride.

I Full and partial inverse agonists inhibit the action of GABA. They act in the opposite way to a typical BDZ and reduce Cl" influx. There are no clinically useful dmgs in this category at present. However, in patients with panic disorder, flumazenil may act like a partial inverse agonist and cause an increase in anxiety symptoms. 

Benzodiazepine partial inverse agonists display weak negative intrinsic activity and act as mild GABA-A receptor antagonists (Haefely, 1994). One such agent, Rol5-4513, ameliorates the symptoms of HE in rats with thioacetamide-induced... 

Maksay, G., Thompson, S. A., and Wafford, K. A. (2000) Allosteric modulators affect the efficacy of partial agonists for recombinant GABA(A) receptors. Br. J. Pharmacol. 129, 1794-1800. 

Hansen, S. L Ebert, B., Fjalland, B., and Kristiansen, U. (2001) Effects of GABA(A) receptor partial agonists in primary cultures of cerebellar granule neurons and cerebral cortical neurons reflect different receptor subunit compositions. Br. J. Pharmacol. 133, 539-549. 

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