A comparative study of aminophylline and acepifylline on reversal phenomenon of anticonvulsant drug efficacy in electroshock model of seizures in rats.

Abstract

The study was designed to compare the proconvulsive activity of two theophylline-containing bronchodilating agents, aminophylline and acepifylline and their antagonistic effects to diazepam, phenytoin, MK-801 and carbamazepine in electroshock seizure model in rats. Graded intensity (30-150 mA for 0.2 s) of electroshock was applied to different groups of rats pretreated either with normal saline (0.5 ml, i.p.), graded doses (25-150 mgkg-1, i.p.) of aminophylline, graded doses (70-560 mgkg-1, i.p.) of acepifylline, graded doses of the antiseizure drugs or to rats pretreated with aminophylline (25 mgkg-1, i.p.) + antiseizure drugs or acepifylline (70 mgkg-1, i.p.) + antiseizure drugs. CI 50 +/- s.e.m. value was 88.41 +/- 2.14 mA in saline treated rats. In aminophylline pretreated rats the values were 84.14 +/- 2.03, 68.06 +/- 1.24, 54.28 +/- 1.96 and 39.58 +/- 2.31 mA at 25 mgkg-1 (0.06 mmolekg-1), 50 mgkg-1 (0.12 mmolekg-1), 100 mgkg-1 (0.24 mmolekg-1) and 150 mgkg-1 (0.36 mmolekg-1), i.p. doses respectively. The values were 85.73 +/- 1.09, 64.86 +/- 2.37, 61.58 +/- 1.37 and 60.62 +/- 2.41 mA at 70 mgkg-1 (0.125 mmolekg-1), 140 mgkg-1 (0.25 mmolekg-1), 280 mgkg-1 (0.50 mmolekg-1) and 560 mgkg-1 (1.0 mmolekg-1), i.p. doses respectively for the acepifylline pretreated groups of rats. Diazepam, MK-801, phenytoin and carbamazepine significantly antagonized electroshock-induced seizure in a dose-dependent manner. Subsensitizing dose of aminophylline (25 mgkg-1, i.p.) but not that of acepifylline (70 mgkg-1, i.p.) pretreatment significantly antagonized the efficacy of all the antiseizure drugs. The study highlighted that acepifylline might be safely used in epileptic patients well controlled on antiepileptic drugs. Aminophylline, on the other hand, should be avoided since it might produce breakthrough seizure attacks due to its greater proconvulsive and anti-antiseizure drug effects.

• Authors: A Chakrabarti
• Journal: Bollettino chimico farmaceutico (Boll Chim Farm) 2000 Nov-Dec Vol. 139 Issue 6 Pg. 270-5 ISSN: 0006-6648 [Print] Italy
• PMID: 11213435 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anticonvulsants
• Bronchodilator Agents
• acefyllin piperazinate
• Aminophylline
• Theophylline

Topics

• Aminophylline (pharmacology)
• Animals
• Anticonvulsants (antagonists & inhibitors, pharmacology)
• Bronchodilator Agents (pharmacology)
• Electroshock
• Male
• Rats
• Rats, Sprague-Dawley
• Seizures (prevention & control)
• Theophylline (analogs & derivatives, pharmacology)