GABA-Activated Ligand Gated Ion Channels:  Medicinal Chemistry and Molecular Biology

Potentiation of the Response of GABAA Receptors by Bangladeshi Medicinal Plants

“…The possibility cannot be excluded that the extracts inhibit the decomposition of pentobarbital in the liver and thus increase sleeping time in mice, but it is unlikely as these plants have been used as traditional medicines for a long time and no toxicity has been reported. These extracts have considerably less effect on GABA A receptors than synthetic drugs such as benzodiazepine and pentobarbital (Nicholls, 1994;Chebib & Johnston, 2000;Harrison et al, 2000), but their side effects may also be much weaker. Thus, when consumed they will induce only slight mental relaxation and pose little risk.…”

“…These heteropentamers composed of various α, β, γ, δ and ε subunits were found to be expressed in Xenopus laevis oocytes (Trauner et al, 2008). The potentiation of the response of these receptors by drugs such as benzodiazepine, pentobarbital and anesthetics induces tranquilizing, sleepinducing or anesthetic responses in humans (Nicholls, 1994;Chebib & Johnston, 2000;Harrison et al, 2000). It was found that fragrant compounds such as terpinen-4-ol, 1-octen-3-ol, and linalool potentiated the response of GABA A receptors expressed in Xenopus oocytes after injection of the receptor poly(A) + RNA or cRNA (Aoshima & Hamamoto, 1999;Aoshima et al, 2001;Aoshima et al, 2006;Hossain et al, 2002aHossain et al, , 2004Hossain et al, , 2007Hossain et al, 2002b).…”

Ion Channels as Drug Targets in Central Nervous System Disorders

“…GABA acts by binding to two different types of receptors, ionotropic receptors (GABA A and GABA c ) and metabotropic receptors (GABA B ). Two GABA receptors subfamilies GABA A and GABA C differ in their ability to form endogenous heteromeric and homomeric receptors and in their physiological and pharmacological properties [343].…”

Novel Cyclic Phosphinic Acids as GABAC ρ Receptor Antagonists: Design, Synthesis, and Pharmacology

“…GABA A and GABA C receptors are ionotropic receptors, belonging to the Cys loop family of ligand-gated ion channels, which also incorporates nicotinic acetylcholine, strychnine-sensitive glycine, serotonin type 3, and some invertebrate anionic glutamate receptors. 1,2 Both GABA A and GABA C receptors are chloride channels that mediate fast synaptic inhibition when activated by GABA. In contrast, GABA B receptors are members of the family 3 class metabotropic receptors; these receptors couple via G proteins (G i/o ) to interact with inwardly rectifying potassium (GIRK) and voltage-gated calcium channels, mediating slow, longer lasting synaptic inhibition by increasing potassium and decreasing calcium conductances.…”

“…3 The GABA C receptor has distinct pharmacology, physiology, and subunit composition to that of GABA A and GABA B receptors. 1,5,6 Consisting of homo-oligomeric or pseudohomooligomeric pentameric compositions of F subunits (F 1 , F 2 , and F 3 subunits) in mammals, 5,7 the receptors are highly expressed in many parts of the brain, including the superior colliculus, 8 cerebellum, 9 hippocampus (high F 2 subunit expression), 10 and, most prominently, the retina (high F 1 subunit expression). 11 The first selective GABA C receptor antagonist developed was 1,2,5,6-tetrahydropyridine-4-yl-methyl-phosphinic acid 3 (TPMPA 3, Figure 1).…”