The in vitro and in vivo pharmacological activity of Boiga dendrophila (mangrove catsnake) venom N. G. Lumsden 1 , B. G. Fry 2 , S. Ventura 3 , R. M. Kini 4 & W. C. Hodgson 1 1 Monash Venom Group, Department of Pharmacology, Monash University, Clayton, Vic. 3800, 2 Australian Venom Research Unit, Department of Pharmacology, University of Melbourne, Melbourne, Vic. 3010, 3 Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville, Vic. 3052, Australia and 4 Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore 117543 1 Summary 1 The great taxonomic and prey base diversity of colubrids (non-front-fanged snakes) suggests that their venoms may represent a Ôliteral gold mineÕ for scientists eager to find novel pharmacological probes (Mackessy, 2002). 2 While pharmacological characterization is lacking for most of these venoms, this is even more so with regard to activity of colubrid venoms on the mammalian autonomic nervous system. This study characterizes the activity of venom from the colubrid, Boiga dendrophila using in vitro smooth muscle preparations and the anaesthetized rat. 3 In the prostatic segment of the rat vas deferens, cumulative additions of venom (1–150 lg ml )1 ) induced concentration-dependent inhibition of electrically evoked (0.2 Hz, 0.3 ms, 70–100 V) twitches. The inhibitory effect of venom (100 lg ml )1 ) was attenuated by 8-phenyltheophylline (8-PT) (20 lM) and 8-cyclopentyl-1, 3-dipropylxanthine (20 lM) but not idazoxan (1 lM), or a combination of ranitidine (0.2 lM) and thioperamide (10 lM). The inhibitory effect of venom (100 lg ml )1 ) was augmented by dipyridamole (10 lM) but abolished by pretreatment with adenosine deaminase (7.5 units/100 ll) suggesting that it contains components with adenosine A 1 receptor activity, most likely adenosine. 4 In isolated segments of guinea-pig ileum, venom (10–100 lg ml )1 ) caused concentration- dependent contractions which were inhibited by the muscarinic receptor antagonist atropine (0.1 lM) but not by the histamine receptor antagonist mepyramine (0.5 lM). 5 In the anaesthetized rat, venom (5–7.5 mg kg )1 , i.v.) caused a hypotensive effect. 6 Our data suggest that the venom contains components with purinergic and muscarinic receptor activity. Keywords: anaesthetized rat, colubrid, guinea-pig ileum, rat vas deferens, snake, venom Introduction The colubrid assemblage (non-front-fanged snakes) includes a diverse array of families and genera within the Colubroidea superfamily (advanced snakes) (McDowell, 1987; Cadle, 1988; Knight & Mindell, 1994; Heise, Maxson, Dowling & Hedges, 1995; Kraus & Brown, 1998; Vidal, Kindl, Wong & Hedges, 2000; Vidal & Hedges, 2002). Due to a relatively inefficient venom deliv- ery system, compared with the hypodermic-like fangs of the atractaspidid, elapid and viperid families, it has been assumed that most colubrids pose little risk to humans (Kardong & Lavin- Murcio, 1993) and therefore most of their venoms have remained uncharacterized. However, there is a growing interest in colubrid venoms as their extensive evolutionary history and prey base suggests that they may represent a vast source of novel toxins and biological activities (Mackessy, 2002). It is also envisaged that further research will help address unanswered questions regarding the biological role of colubrid venoms. Most studies which have investigated colubrid venoms have focused upon toxicity determina- tion, biochemical characterization (e.g. protease and phospholipase activities) and activities affect- ing haemostasis (for a review see Mackessy, 2002). Only two studies (Young, 1992, 1996) examining the action of colubrid venoms upon the autonomic nervous system, rather than the somatic division (Levinson, Evans & Groves, 107 Autonomic & Autacoid Pharmacology, 24, 107–113 Ó 2004 Blackwell Publishing Ltd Correspondence: W. C. Hodgson