ReceptoPharm, Inc.

The use of snake venom in the treatment of multiple sclerosis has been, at best, controversial. The anecdotal reports for snake venom's beneficial effects in this condition may be supportable now by recent scientific evidence. Cobratoxin, a neurotoxin obtained from the venom of the Thailand cobra, has demonstrated several pharmacological activities that strongly support its use in this application. By employing a chemical detoxification step, the neurotoxin can be rendered safe for administration to humans with minimal side effects. This modified neurotoxin has demonstrated neuromodulatory, antiviral, and analgesic activity, elements associated with the multiple sclerosis condition. Modified cobratoxin has demonstrated potent immunosuppressive activity in acute and chronic animal models of the disease. The drug is under investigation for use in adrenomyeloneuropathy and clinical trials in Multiple sclerosis are planned.

Objective To investigate the analgesia induced by receptin (REC), a chemically modified cobratoxin (CTX, a long-chain postsynaptic alpha -neurotoxin from Thailand cobra venom), and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally (5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.) or intra-cerebral venticularly (62.5 mu g/kg, i.c.v.). The antinociceptive action was determined using the hot-plate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine (Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.) or naloxone (Nal; 3 mg/kg, i.p.). The effect of REC on motor activity was tested using the Animex test in mice. Results REC (5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.) exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 mu g/kg (1/160 of systemic dose; i.c.v.) produced marked analgesic effects. Atropine at 0.5 mg/kg (i.m.), 10 mg/kg (i.p.) or naloxone at 3 mg/kg (i.p.) failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC' s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.

Pain has been called the fifth vital sign, and chronic pain impacts the lives of millions. The search for better analgesics is at a fever pitch, but opiates still dominate the moderate to severe pain treatment spectrum, and morphine, essentially a 2000-year-old drug, is still the gold standard. By today's pharmaceutical standards, opiates are old hat, and physicians are generally reluctant to prescribe them due to their potential for adverse effects and abuse. It is suggested that a new look at another old solution, cobra venom, could inject new life into pain management. This review looks at the historical use of cobra venom to control moderate to severe pain and at recent understandings of its mechanism of action.