Lack of anticonvulsant tolerance with RU 32698 and Ro 17-1812.
Possible development of anticonvulsant tolerance to three benzodiazepine receptor ligands was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. Extensive tolerance developed rapidly in the case of diazepam (0.35 mg/kg b.d. or 1.5 mg/kg b.d.). No significant tolerance was seen with the imidazopyrimidine derivative RU 32698 (9 mg/kg b.d.) or the partial agonist benzodiazepine Ro 17-1812 (1 mg/kg b.d.) These results provide further support for the hypothesis that partial agonists at the benzodiazepine receptor induce less tolerance than full agonists.
Department of Pharmacology, University of Leeds, U.K.
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M
Feely
P
P
Boyland
A
A
Picardo
A
A
Cox
J P
JP
Gent
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004361:Drug Tolerance; D007093:Imidazoles / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D011743:Pyrimidines / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D001570:Benzodiazepinones; D007093:Imidazoles; D011743:Pyrimidines; C060714:divaplon; C049715:Ro 17-1812; D003975:Diazepam; D010433:Pentylenetetrazole