A novel neuronal nicotinic acetylcholine receptor agonist with cognition enhancing and anxiolytic activities.

Prod. No. A 6476

Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated cation channels that are activated by the alkaloid (–)-nicotine (Prod. No. N3876) and are classified on the basis of their subunit structure [1]. Ten a (a1- a10) and four b ( b1-b4) subunits have been cloned from mammalian and avian sources. Additional g, d and e subunits are associated with nAChRs present at the neuromuscular junction [1-3]. Until recently, few selective ligands have been widely available with which to study nAChRs. Such compounds include the sedative a4b2 antagonist dihydro-b -erythroidine (Prod. No. D-149) and the selective a7 antagonists methyllycaconitine
(Prod. No. M-168) and MG-264 (Prod. No. M3184).

Sigma-RBI is pleased to introduce ABT 418 (Prod. No. A6476) as a novel bioisostere of (–)- nicotine that is a full agonist at the a4b2 neuronal nAChR, which is a predominant form of nAChR in the central nervous system (CNS).

Features and Benefits:

• Potent displacer of [³H]-cytisine binding to rat brain nAChRs (K_i = 3 nM) [3].
• Essentially inactive (K_i > 10 µM) in a wide range of other receptor/neurotransmitter uptake/enzyme assays, including those for muscarinic and 5-HT₃ serotonin receptors [3].
• Demonstrated a reduced potency at the subunit isoforms of nAChR found in sympathetic ganglia as compared with (–)-nicotine [4,5].
• Improved retention of inhibitory avoidance training in rodent behavioral tests, with less undesirable side effects such as emesis, hypothermia and seizures [4,5].

Physical Description: Solubility: Molecular Formula: Formula Weight: Sizes:

Solid Soluble at 15 mg/ml in water C9H14N2O•HCl 202.7 5 mg, 25 mg

Subject to U.S. Patent No. 5409946 and sold under license from Abbott Laboratories.

References

1. Lukas, R.J. et al., Pharmacol. Rev., 51, 397-401 (1999).
2. Lloyd, K.G. and Williams, M., J. Pharmacol. Exp. Ther., 292, 461-467 (2000).
3. Dani, J.A., Biol. Psychiatry, 49, 166-174 (2001).
4. Decker, M.W. et al., J. Pharmacol. Exp. Ther., 270, 319-328 (1994).
5. Brioni, J.D. et al., J. Pharmacol. Exp. Ther., 271, 353-361 (1994).

To order, please call 800-325-3010 or Fax 800-325-5052 or contact your local Sigma-Aldrich sales office. On-line ordering is not yet available for this product.

ABT 418 is featured in Celltransmissions Volume 19, No. 1. Click here to see article.

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