A comparative study of aminophylline- and acepifylline-induced seizures and death in the chemoconvulsion model in rats.
The convulsive, pro-convulsive and lethal effects of two theophylline-containing bronchodilating agents, aminophylline and acepifylline, have been evaluated in rats. Aminophylline (theophylline ethylenediamine) caused seizures and death in a dose-dependent manner; an intraperitoneal dose of 250 mg kg-1 caused seizures and death in all rats. Intraperitoneal doses of acepifylline (theophylline ethanoate of piperazine) up to 1000 mg kg-1, however, did not cause seizure or death. Further, pre-treatment of the rats by intraperitoneal administration of a subconvulsive dose (100 mg kg-1) of aminophylline caused a significant decrease in CD50 and LD50 values for pentylenetetrazole and a significant increase in the number of positive responders (i.e. rats with a pentylenetetrazole-induced seizure score of 3 or more on a seizure scale ranging from 0 to 6) and death rate compared with those obtained for rats pre-treated with an equivalent intraperitoneal dose (140 mg kg-1) of acepifylline ('equivalent dose' referred to here denotes the theophylline content of the two preparations). The study has established the neurosafety profile of acepifylline and documents a safer alternative to aminophylline for use in asthmatics suffering from concomitant epilepsy or other seizure-prone neurological defects.
Chakrabarti
A
A
Department of Pharmacology, Indira Gandhi Medical College, Himachal Pradesh, India.
Saini
H K
HK
Garg
S K
SK
D000628:Aminophylline / Q000633:toxicity*; D000818:Animals; D001993:Bronchodilator Agents / Q000633:toxicity*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004347:Drug Interactions; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced*; D013806:Theophylline / Q000031:analogs & derivatives* / Q000633:toxicity
D001993:Bronchodilator Agents; D003292:Convulsants; C023721:acefyllin piperazinate; D000628:Aminophylline; D013806:Theophylline; D010433:Pentylenetetrazole