CL 218872 antagonism of diazepam induced loss of righting reflex: evidence for partial agonistic activity at the benzodiazepine receptor.
A recent hypothesis suggests that the "selective anxiolytic" activity of the triazolopyridazine, CL 218872, is a reflection of this compounds high affinity for a benzodiazepine (BZD) receptor subtype. Subsequent to this proposal, the observation was made that CL 218872 does not effectively discriminate BZD receptor subtypes in vitro at physiological temperatures (37 degrees C). Based upon this observation, a selective effect in vivo related to the high affinity of CL 218872 for a BZD receptor subtype appears unlikely. The present study provides evidence for an alternative hypothesis to explain the unique pharmacological properties of CL 218872. The ability of CL 218872 to antagonize diazepam induced loss of righting reflex and enhance the anticonvulsant effect of diazepam in mice suggests that this triazolopyridazine may act as a partial agonist at the BZD receptor. Compared to the pharmacologically active BZDs, the unique actions of CL 218872 may be related to the lower intrinsic activity of this compound.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003975:Diazepam / Q000037:antagonists & inhibitors*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D011187:Posture; D011724:Pyridazines / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A; D012018:Reflex / Q000187:drug effects*
D000927:Anticonvulsants; D011724:Pyridazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; C021604:CL 218872; D003975:Diazepam