Details

Autor(en) / Beteiligte

• Rowlett, James K
• Platt, Donna M
• Lelas, Snjezana
• Atack, John R
• Dawson, Gerard R

Titel

Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2005-01, Vol.102 (3), p.915-920

Ort / Verlag

United States: National Acad Sciences

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• Benzodiazepines exert their effects by binding to multiple subtypes of the GABA A receptor, the predominant subtypes in the brain being those that contain α 1 -, α 2 -, α 3 -, and α 5 -subunits. To understand the potentially different roles of these subtypes in the therapeutic and side effects of benzodiazepines, we evaluated GABA A receptor subtype-preferring compounds in nonhuman primate models predictive of anxiolytic, sedative, motor, subjective, and reinforcing effects of benzodiazepine-type drugs. These compounds included zolpidem, which shows preferential binding to GABA A receptors containing α 1 -subunits (α 1 GABA A receptors); L-838,417, which shows functional selectivity for α 2 GABA A , α 3 GABA A , and α 5 GABA A receptors; and nonselective conventional benzodiazepines. The results provide evidence in nonhuman primates that α 1 GABA A receptors do not play a key role in the anxiolytic and muscle-relaxant properties of benzodiazepine-type drugs; instead, these effects involve α 2 GABA A , α 3 GABA A , and/or α 5 GABA A subtypes. Our results also suggest that the α 1 GABA A receptor subtype might be critically involved in the subjective, sedative, and motor effects of benzodiazepine-type drugs. In contrast, stimulation of α 1 GABA A receptors is sufficient, but not necessary, for mediation of the abuse potential of these drugs. addiction anxiety