CIRCADIAN VARIATION OF THE ACUTE TOXICITY AND NOCICEPTIVE ACTIVITY OF AMINOPHYLLINE IN MICE

The circadian variation of the toxicity and nociceptive actIvity of aminophylline as an important methylxanthine was studied in mice. The animals were housed under controlled light-dark cycles for at least 2 weeks. Acute toxicity was determined by LD50. Hot-plate test was used for determination of thermal pain threshold. Doses of 200, 250, 280 and 340 mg/kg of aminophylline were injected intraperitoneally to four separate groups of six male mice at six hour intervals (09:00,15:00,21:00,03:00). Mortality was recorded at 1,24, and 48 hours after injection and LD50 value was measured by logit method after 48 hours. The results showed that the lowest nociceptive effect was at the beginning of the dark phase. The lowest LD50 value was also at the beginning of the dark phase. This study indicated that the toxicity of aminophylline was maximum at night and had a different rhythm pattern of nociceptive activity. This indicates different mechanisms of action for these effects.