CHAPTER 5. Reptile Venoms as a Platform for Drug Development

Haemotoxic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

“…It achieved US Food and Drug Administration approval in the early 1980's, subsequently becoming Squibb's first billion dollar drug, and the success of this product resulted in the development of many analogues (e.g. enalapril, lisinopril, perindopril and ramipril) being introduced into the market (Smith & Vane, ; McCleary et al , ).…”

“…Both these disintegrins exhibit potent inhibition of the integrin receptor α 2 β 3 , thereby preventing the aggregation of platelets. Both toxins were developed synthetically; as a non‐peptidic molecule in the case of Tirofiban and as a cyclic heptapeptide analogue for Eptifibatide (McCleary et al , ). Consequently, these anticoagulant therapeutics function by effectively inhibiting platelet aggregation and they are indicated for use in patients suffering from unstable angina and myocardial infarctions (Peerlinck et al , ; Scarborough, ).…”

“…Batroxobin is a drug developed from a serine protease toxin (SVSP) isolated from the venom of the Brazilian lancehead viper ( Bothrops moojeni ). As with many SVSPs, this enzymatic toxin exhibits potent specificity for fibrinogen, in this case effectively releasing fibrinopeptide A via cleavage of the α‐chain of fibrinogen (McCleary et al , ). Such thrombin‐like SVSP enzymes also benefit from not being inhibited by classical serine protease inhibitors, whether endogenous (e.g.…”

“…antithrombin III) or exogenous (e.g. hirudin) (Hutton & Warrell, ; McCleary et al , ). Although the fibrinogenolytic activity of batroxobin initially promotes the formation of clots, it is an anticoagulant drug of relevance for treating thrombotic disorders, as the degradation of fibrinogen leads to defibrination and, secondarily and indirectly, this in turn induces the release of tissue plasminogen activator, which converts plasminogen into plasmin and promotes the degradation of clots (McCleary et al , ).…”

“…hirudin) (Hutton & Warrell, ; McCleary et al , ). Although the fibrinogenolytic activity of batroxobin initially promotes the formation of clots, it is an anticoagulant drug of relevance for treating thrombotic disorders, as the degradation of fibrinogen leads to defibrination and, secondarily and indirectly, this in turn induces the release of tissue plasminogen activator, which converts plasminogen into plasmin and promotes the degradation of clots (McCleary et al , ). Specific indications for batroxobin include the treatment of ischaemic stroke, angina, myocardial and cerebral infraction and wound management after surgical interventions (Xu et al , ; Phillips et al , ).…”