GabaA ligand structures

HT3 receptors belong to the ligand-gated ion channel receptor superfamily, similar to the nicotinic acetylcholine or GABAa receptors and share elec-trophysiological and structural patterns. The receptors... 

Figure 11.6 Schematic representation of the GABAa receptor complex. Examples of the many structurally diverse compounds that act at different sites on the receptor (see text for details). Picrotoxinin, the active component of picrotoxin, and TBPS act as non-competitive antagonists. The barbiturates, steroids and anaesthetics are positive allosteric modulators, as are the benzodiazepine site ligands shown, with the exception of DMCM (negative allosteric modulator) and flumazenil (benzodiazepine site antagonist)...

Neuro steroids, which may be physiological modulators of brain activity, enhance GABAa receptor function 297 The three-dimensional structures of ligand-gated ion channel receptors are being modeled successfully 297 Mouse genetics reveal important functions for GABAa receptor subtypes 297... 

DEVELOPMENT OF LIGANDS FOR THE GABAa RECEPTOR USING MUSCIMOL AS A LEAD STRUCTURE... 

Hydrophobicity (log P) is related to the desolvation of the ligand, and it is assumed that the desolvation of the ligands going from water to octanol parallels that of going from water to a cleft or pocket of a receptor. Thus, log P may be an important term in establishing quantitative relationships between structure and activity (26). In order to examine the influence of the lipohilic character of the 4-PIOL analogs on the affinity for the GABAa receptor, QSAR analysis was performed (24). 

Fig. 1 Structures of subunits (top) and subunit oligomerization (bottom) in ligand-gated ion channels. (a) P2X receptor family, (b) Ionotropic glutamate receptor family, (c) TRPV channel family, (d) Cys-loop superfamily comprising nAChRs, 5-HT3,GABAa, and glycine receptors.

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