(±)-Epibatidine dihydrochloride hydrate 

The activity of epibatidine at neuronal and neuromuscular nicotinic acetylcholine receptors was compared with the activity of nicotine and suxamethonium. Activation of ganglionic nicotinic receptors by epibatidine was shown in the guinea-pig ileum (contraction mediated by the cholinergic neurons of the ileum) and in pithed and atropinized rats (rise in blood pressure). Epibatidine also activated nicotinic receptors at the peripheral terminals of afferent C-fibres (rabbit ear) and in the brain (antidiuresis in rats). The agonistic effects of epibatidine were followed by long-lasting receptor desensitization. No antinociceptive effect of epibatidine was seen in rats at a dose free of motor impairment. On muscle end plate nicotinic receptors of the rat diaphragm (not responding to depolarizing agents by contraction), epibatidine was equipotent with suxamethonium in causing neuromuscular inhibition. On an extraocular muscle of the rabbit (responding to depolarizing agents by contraction) epibatidine in vitro and in situ caused a contraction at a 100-fold lower dose than suxamethonium. The Straub tail reaction in mice to epibatidine could be attributed to the sustained stimulation of motor end plate receptors of the "slow contracting" type of muscle fibres by epibatidine. Epibatidine was the most potent agonist on all neuronal and neuromuscular nicotinic receptors examined.

≥98% (HPLC)

powder

off-white

DMSO: >4 mg/mL

methanol: 4 mg/mL

Decker, M.W., and Meyer, M.D., Therapeutic potential of neuronal nicotinic acetylcholine receptor agonists as novel analgesics. Biochem. Pharmacol. 58, 917-923, (1999) abstract

Sihver, W., et al., Autoradiographic comparison of [³H](−)nicotine[³H]cytisine and [³H]epibatidine binding in relation to vesicular acetylcholine transport sites in the temporal cortex in Alzheimer's disease. Neuroscience 94, 685-696, (1999) abstract

Lembeck, F, Epibatidine: high potency and broad spectrum activity on neuronal and neuromuscular nicotinic acetylcholine receptors. Naunyn Schmiedebergs Arch. Pharmacol. 359, 378-385, (1999) abstract

UN 2811 6.1/PG 1

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