Anticonvulsant activity of pyrrolo[1',2':1,2]imidazo[4,5-b]pyridines, pyrrolo[2',1':2,3]imidazo[4,5-c] pyridines and pyrrolo[2,1-f]purines in DBA/2 mice.
1. The behavioural and anticonvulsant effects of eight pyrroloimidazopyridines (PI1a-d and PI2a-d) and four pyrrolopurines (PP) were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated in DBA/2 mice on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. 3. Hypothermic activity was observed after the highest doses of the pyrroloderivatives studied. 4. Our study demonstrated that the anticonvulsant effect of pyrroloimidazopyridines (PI1-7,8,8a,9-tetrahydro-6H-pyrrolo-[1',2':1,2]imidazo[4,5-b]pyrid in-6- ones) and pyrrolopurines (PP) was generally better than corresponding pyrrolobenzimidazoles (PB) and pyrroloimidazopyridines (PI2-5,5a,6,7-tetrahydro-8H-pyrrolo[2',1':2,3]imidazo[4,5-c]pyridin-8- ones) and, in some cases, comparable to that of phenytoin and desmethylclobazam. 5. The anticonvulsant potency of the derivatives studied cannot be directly related to their lipophilicity.
De Sarro
A
A
Chair of Chemotherapy, Faculty of Medicine, University of Messina, Italy.
De Sarro
G
G
Chimirri
A
A
Grasso
S
S
Monforte
A M
AM
Zappalà
M
M
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D011687:Purines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D011687:Purines; D011725:Pyridines