A sleep inducing factor from common Indian toad (Bufo melanostictus, Schneider) skin extract Manika Das a , B.N. Mallick b , S.C. Dasgupta a, 1 , A. Gomes a, * a Laboratory of Toxinology and Experimental Pharmacodynamics, Department of Physiology, University of Calcutta, 92, A.P.C. Road, Calcutta 700 009, India b Department of Neurobiology, School of Life-Science, Jawaharlal Nehru University, New Delhi 110067, India Received 15 April 1999; accepted 18 October 1999 Abstract Bufo melanostictus (common Indian toad) acquire dierent bioactive substances in their skin during their life-time in wide ecological habitat. Earlier investigation from this laboratory revealed that toad (B. melanostictus ) skin extract (TSE) posses dierent bioactive compounds of dierent diversity (Das, M., Auddy, B. and Gomes, A., 1996. Pharmacological study of the toad skin extract on experimental animals. Indian J. Pharmacol. 28, 72±76). Among these sleep induction and sleep potentiation indicated the possibility of sleep inducing factor(s) in TSE. One such sleep inducing factor (SIF) was isolated and puri®ed by neutral alumina column chromatography followed by HPLC. Spectroscopy (UV, IR, FAB-MASS) study indicated that the sleep inducing factor was a 880 Dalton conjugated aromatic compound with a hydroxyl and carbonyl functional group. Biological study showed that SIF produced no lethality in male albino mice upto the dose of 8 mg/kg, i.v. Cyproheptadine antagonised SIF induced contraction of isolated smooth muscle indicating histamine/serotonin receptor mediated action of SIF. EEG studies showed that SIF increased sleep and decreased awakening condition of freely moving rats. Biochemical studies showed that SIF produced signi®cant alteration of brain biogenic amine levels, monoamine oxidase (MAO) and tryptophan hydroxylase (TH) activity. This 0041-0101/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0041-0101(99)00229-9 Toxicon 38 (2000) 1267±1281 www.elsevier.com/locate/toxicon 1 Present address. Department of Zoology, Moulana Azad College, Calcutta 700013, India. * Corresponding author. Fax: +91-33-351-3755. E-mail address: agomes@cucc.ernet.in (A. Gomes).