Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.
S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg/kg, p.o. and 15.0 (10.2-23.7) mg/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg/kg, s.c.) or bemegride (40 mg/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy.
Discovery Research Laboratories II (Aburahi), Shionogi & Co., Ltd., Shiga, Japan.
M
M
Eigyo
T
T
Shiomi
Y
Y
Inoue
I
I
Sakaguchi
C
C
Ishibashi
S
S
Murata
K
K
Koyabu
A
A
Matsushita
I
I
Adachi
M
M
Ueda
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001534:Bemegride / Q000008:administration & dosage / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004597:Electroshock; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity; D010852:Picrotoxin / Q000008:administration & dosage / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D000927:Anticonvulsants; D001534:Bemegride; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016202:N-Methylaspartate; D010433:Pentylenetetrazole; D010852:Picrotoxin; C059447:S 312