AHR-12245: a potential anti-absence drug.
AHR-12245, 2-(4-chlorophenyl)-3H-imadazo[4,5-b]pyridine-3-acetamid, ethosuximide, Na valproate, phenytoin, and clonazepam were evaluated in mice and rats with a battery of well-standardized anticonvulsant test procedures. The results obtained indicate that the anticonvulsant profile of AHR-12245 is similar to that for ethosuximide and clonazepam. AHR-12245 is effective in nontoxic intraperitoneal doses in mice by the maximal electroshock seizure (MES), pentylenetatrazol (s.c. PTZ), bicuculline, and picrotoxin tests but ineffective against strychnine-induced seizures; it is effective after nontoxic oral doses in both mice and rats by the s.c. PTZ test and ineffective by the MES test. The candidate antiepileptic substance was also ineffective against seizures induced in amygdala and corneally kindled rats. The PIs for AHR-12245 by the s.c. PTZ test were 4.5 to 12 times higher than those for the prototype agents, except that for clonazepam when administered orally in mice. The in vitro studies indicate that AHR-12245 is a weak inhibitor of benzodiazepine (BDZ) receptor binding but does inhibit adenosine uptake. These results indicate that AHR-12245 is a relatively nontoxic agent with a profile of anticonvulsant action which suggests it should be useful in generalized absence seizures.
Johnson
D N
DN
A.H. Robins Research Laboratories, Richmond, VA.
White
H S
HS
Swinyard
E A
EA
Albertson
T E
TE
Kilpatrick
B F
BF
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D004341:Drug Evaluation; D004832:Epilepsy, Absence / Q000503:physiopathology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D007696:Kindling, Neurologic; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000209:etiology / Q000503:physiopathology
D000927:Anticonvulsants; D007093:Imidazoles; D009498:Neurotoxins; D011725:Pyridines; C069610:2-(4-chlorophenyl)-3H-imidazo(4,5-b)pyridine-3-acetamide