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Epibatidine and derivatives

Abbott Laboratories began working with epidatidine in an effort to develop similar compounds with applications for treating pain in humans. Abbott Labs eventually created ABT-594, a non-toxic, nonaddictive painkiller potentially effective for treating several types of pain. Unlike an opiate, ABT-594 "promotes alertness instead of sleepiness and has no side effects on respiration or digestion" [Wilson 2002].


http://www.mongabay.com/05epidatidine.htm
 
Uck. Non addictive my ass. Neither is Nicotine if you buy what Phillip-Morris has to say. Neither is this if you buy what Abbot has to say. Epibatidine is not something I'd touch. It's far too toxic.

As far as ABT-594? I doubt it's non-addictive either (or all that non-toxic, but I'm sure it's much less than the other two), but if it's longer lasting, it'd produce a greatly reduced dependence, I'm sure.

They should keep these shit nicotinic drugs where they can be of real value: treating Parkinson's Disease and Alzheimers (Nicotine was found to be equally effective as Donepezil).

We've got really good drugs for treating pain of all types. I don't know why they'd look at these sorts of drugs for pain.
 
ABT-594 was dropped from clinical trials at phase 2 as far as I remember, because of unacceptable side effects, can't remember what though, I'll look it up. Think it produced severe nausea and vomiting, but in itself that wouldn't normally be enough to drop development so probably there was something rarer but more serious that cropped up as well.

Abbott have actually made heaps of compounds in this series, ABT-094, ABT-418, Epiboxidine, Ispronicline, Rivanicline...no idea if any of them are much better than ABT-594 though, last thing I heard they had dropped that one but still had others in the same series that they were working on, haven't heard any more progress in this area for a couple years though.

There may be many different painkillers available already, but thats no reason not to research new ones, theres always some patient who is in too much pain for NSAIDs but allergic to all opioids for some reason etc, widening the pharmaceutical repertoire can't be a bad thing.
 
Heres a newer one, thought they were still working in this area.

5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) is a novel nicotinic acetylcholine receptor (nAChR) ligand that binds to the agonist-binding site ([3H]-cytisine) with Ki value of 3.1 nM and exhibits agonist selectivity at alpha4beta2 nAChR relative to the alpha3beta4 nAChR subtype. The analgesic effects of A-366833 were examined across a variety of animal models including the mouse model of writhing pain (abdominal constriction), the rat models of acute thermal (hot box), persistent chemical (formalin) and neuropathic (spinal nerve ligation, SNL) pain. In the abdominal constriction model, A-366833 was effective at doses ranging from 0.062 to 0.62 micromol/kg (i.p.). In addition, A-366833 demonstrated significant effects in acute thermal pain (6.2-19.0 micromol/kg, i.p.), formalin (1.9-19 micromol/kg i.p.) and SNL (1.9-19 micromol/kg i.p.) models. The systemic effects of A-366833 were attenuated by pretreatment with mecamylamine (5 micromol/kg i.p.) in both the formalin and SNL models, suggesting that the analgesic effects of A-366833 in models of persistent nociceptive and neuropathic pain are mediated by activation of nAChRs. Pharmacokinetic investigations of A-366833 in rat revealed moderate brain:plasma distribution, half-life of 1.5h and excellent oral bioavailability of 73%. Comparison of peak plasma levels at the minimal effective doses across rat models of acute thermal pain, formalin and SNL with the maximal exposure that does not evoke emesis in ferret revealed therapeutic margins ranging from 6- to 22-fold. These studies indicate that compounds like A-366833 with improved agonist selectivity at alpha4beta2 vs. alpha3beta4 nAChR can elicit a broad spectrum of analgesic efficacy without concurrent adverse effects.
Click to expand...

Ji J, Bunnelle WH, Anderson DJ, Faltynek C, Dyhring T, Ahring PK, Rueter LE, Curzon P, Buckley MJ, Marsh KC, Kempf-Grote A, Meyer MD. A-366833: a novel nicotinonitrile-substituted 3,6-diazabicyclo[3.2.0]-heptane alpha4beta2 nicotinic acetylcholine receptor selective agonist: Synthesis, analgesic efficacy and tolerability profile in animal models. Biochem Pharmacol. 2007 Oct 15;74(8):1253-62.
 
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