Abdel-Fattah Mohamed Abdel-Fattah (1,2), Kinzo Matsumoto (1), Yukihisa Murakami (1), Kawther Abdel-Wahed El-Hady (2), Moustafa Fayez Mohamed (2) and Hiroshi Watanabe (1,*)
(1) Division of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-01, Japan (2) Pharmacology and Toxicology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt (*) To whom all correspondence should be addressed.
Abstract: The effects of harmaline on tryptophan-induced 5-hydroxytryptamine (5-HT) syndrome and body temperature changes in pargyline-pretreated rats were investigated. When administered i.p. 60 min after pargyline treatment (50 mg/kg, i.p.), tryptophan, at 100 mg/kg but not 10 mg/kg, induced the 5-HT syndrome. Tryptophan at 100 mg/kg also produced hypothermia followed by hyperthermia in pargyline-pretreated rats. Administration of harmaline (10 mg/kg, i.p.) 30 min after pargyline not only potentiated the 100 mg/kg tryptophan-induced 5-HT syndrome and body temperature changes, but also produced the syndrome following administration of 10 mg/kg tryptophan in pargyline-pretreated rats. In contrast, when administered 30 min before pargyline, 10 mg/kg harmaline completely suppressed the syndrome and body temperature changes caused by 100 mg/kg tryptophan. Tryptophan (100 mg/kg, i.p.) administration significantly increased 5-HT levels and decreased 5-hydroxyindole acetic acid levels and 5-HT turnover in the brain of pargyline-pretreated rats. Harmaline administration 30 min after pargyline did not significantly affect the tryptophan-induced changes in 5-HT levels and 5-HT turnover, whereas when administered 30 min before pargyline, harmaline significantly blocked the effect of tryptophan. These results suggest that mechanisms underlying the inhibitory action of harmaline on the tryptophan-induced 5-HT syndrome and body temperature changes in pargyline-pretreated rats differ from those by which harmaline potentiates the effects of tryptophan.
Keywords:
Harmaline, Tryptophan, Pargyline, 5-Hydroxytryptamine syndrome, Body temperature