RO 16-6028, a benzodiazepine receptor partial agonist, does not exhibit anticonvulsant tolerance in mice.
The development of anticonvulsant tolerance with RO 16-6028, a benzodiazepine receptor partial agonist, was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. In contrast to other benzodiazepines tested previously in this seizure model the anticonvulsant protection afforded by RO 16-6028 did not change significantly during 10 days treatment (2 mg/kg b.i.d.). This result supports the hypothesis that partial agonists at the benzodiazepine receptor may induce less tolerance and/or dependence than full agonists.
Haigh
J R
JR
University Department of Medicine, University of Leeds, U.K.
Feely
M
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011963:Receptors, GABA-A / Q000187:drug effects*
D000927:Anticonvulsants; D001570:Benzodiazepinones; D011963:Receptors, GABA-A; C054626:bretazenil; D010433:Pentylenetetrazole