Antiseizure activity of insulin: insulin inhibits pentylenetetrazole, penicillin and kainic acid-induced seizures in rats.
The present study was undertaken to evaluate the antiseizure activity spectrum of insulin against various behavioral seizure models in rats. Insulin was injected intraperitoneally (i.p.) at a test dose of 1 U/kg. Dextrose (3 g/kg) was administered simultaneously with insulin to counteract its hypoglycemic effect and induce a normoglycemic state. Insulin was found to significantly decrease the incidence, intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by pentylenetetrazole (60 mg/kg i.p.) and significantly decrease the intensity and mortality rate and prolong the latency of generalized tonic-clonic convulsions induced by penicillin (2000 U/intracerebrocortical). Insulin was not only found to prolong the latency of all the seizure components but was found to reduce the incidence of focal myoclonic twitches and generalized tonic-clonic convulsions induced by kainic acid (12 mg/kg i.p.) as well. Insulin was shown to be ineffective to suppress ouabain (5 micrograms/intracerebroventricular) induced seizures. These findings indicate that insulin possesses a broad spectrum of antiseizure activity in rats. Interaction with brain Na(+)-K(+)-ATPase has been discussed as a possible mechanism of action.
Uysal
H
H
Ministry of Health Ankara Hospital, Clinic of Neurology, Turkey.
Kuli
P
P
Cağlar
S
S
Inan
L E
LE
Akarsu
E S
ES
Palaoğlu
O
O
Ayhan
I H
IH
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003292:Convulsants / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007608:Kainic Acid / Q000037:antagonists & inhibitors; D008297:Male; D010042:Ouabain / Q000037:antagonists & inhibitors; D010406:Penicillins / Q000037:antagonists & inhibitors; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D000927:Anticonvulsants; D001786:Blood Glucose; D003292:Convulsants; D007004:Hypoglycemic Agents; D007328:Insulin; D010406:Penicillins; D010042:Ouabain; D005947:Glucose; D007608:Kainic Acid; D010433:Pentylenetetrazole