General pharmacology of the novel antiepileptic compound zonisamide. 2nd communication: effects on cardiovascular, visceral, renal and blood functions.
The effects of 1,2-benzisoxazole-3-methanesulfonamide (zonisamide, AD-810, CI-912), an antiepileptic compound, on the cardiovascular, visceral, renal and blood functions were compared with those of carbamazepine and, in part, acetazolamide in experimental animals. 1. Zonisamide (30 mg/kg i.v.) transiently lowered the blood pressure and decreased the blood flows in the carotid and femoral arteries in anesthetized dogs. The effects were 3 times less potent than those of carbamazepine, Zonisamide, when orally administered, did not affect the blood pressure even at 300 mg/kg in conscious rats. 2. Zonisamide little affected the autonomic nervous system even at high doses. In anesthetized cats, contractions of the nictating membrane by electrical stimulation of the cervical sympathetic nerve, pressor responses to norepinephrine, and depressor responses to acetylcholine, all were not modified with zonisamide (100 mg/kg i.v.). In isolated guinea-pig ileum, contractions induced by acetylcholine, histamine and bradykinin were not affected by zonisamide up to a concentration of 10(-3) g/ml zonisamide, although those by serotonin and nicotine were depressed with high concentrations over 10(-5) g/ml. 3. With 100 mg/kg p.o., zonisamide decreased the gastric juice volume and pH in pylorus ligated rats, and depressed gastric emptying in rats, but did not inhibit the intestinal transit of charcoal meal in mice. These effects were less potent than those of carbamazepine. 4. Zonisamide increased the urine volume, pH, and Na+ and K+ concentrations in rats and anesthetized dogs. The renal blood flow and glomerular filtration rate were little changed with the high doses of zonisamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakatsuji
K
K
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Matsuno
Y
Y
Nakamura
N
N
Fujitani
B
B
Ito
T
T
Kadokawa
T
T
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D002415:Cats; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000097:blood / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D000078305:Zonisamide
D000927:Anticonvulsants; D007555:Isoxazoles; D010080:Oxazoles; D000078305:Zonisamide