A7 nicotinic receptor agonist

The efficacy of a7-nicotinic receptor agonists has been assessed in multiple animal paradigms of learning and memory. For example, DMXB-A improves monkey performance on a delayed matching to sample task, an effect that persists for 24 h after drug administration (Briggs et al., 1996). DMXB-A... 

Scheme 4.39 Aldol addition of triphenyl glycol ester 173 to bicydic ketone 180 as the key step in a synthesis of the selective a7 nicotinic receptor agonist AR-R17779.

Nicotine is an agonist at the nicotinic acetylcholine receptor (nAChR). Activation of this receptor depolarizes target cells (see Ch. 11). nAChRs are composed of five subunits surrounding a central ion-channel pore. Twelve different nicotinic receptor subunits are expressed in the nervous system (a2-oclO and (32—134). Of these, a subset is expressed in the VTA (a3-a7 and P2—134). It is thought that a7 receptors form homomeric receptors a3, a4 and a6 form heteromeric channels with 02 or 04 and a5 and 03 can associate with other a/0 pairs. Studies in knockout mice implicate several subunits in the ability of nicotine to modulate dopamine neurons (a4, a6, a7, 02, 03) but... 

Tropisetron is marketed outside the U.S. as a 5HT3 receptor antagonist for nausea, but it has a7-nicotinic agonist effects in the same concentration range. Tropisetron normalizes P50 inhibition in schizophrenics, with the effect primarily occurring in the nonsmoking subjects (Koike et al., 2005). 

Boess FG, de Vry J, Erb C, Flessner T, Hendrix M, Luithle J et al (2013) Pharmacological and behavioral profile of N-[(3R)-l-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141), a novel a7 nicotinic acetylcholine receptor agonist/ serotonin 5-HT3 receptor antagonist. Psychopharmacology (Berl) 227 1-17... 

Hibbs RE, Sulzenbacher G, Shi J, Talley TT, Conrod S, Kem WR, Taylor P, Marchot P, Bourne Y (2009) Stmctural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal a7 nicotinic acetylcholine receptor. EMBO J 28 3040-3051... 

Figure 5. Agonist actions of imidacloprid on the wild-type and mutant (Q79E, Q79K ami Q79R) a7 nicotinic acetylcholine receptors expressed in Xenopus oocytes. Abbreviation ACh, acetylcholine, Reproducedfiomref 29with permission of Nature Publishing Group,...

De Fiebre, C.M., Meyer, E.M., Henry, J.C., Muraskin, S.I., Kem, W.R., Papke, R.L., 1995, Characterization of a series of anabaseine-derived compounds reveals that the 3-(4)-dimethylamino-cinnamylidine derivative is a selective agonist at neuronal nicotinic a7/ l-a-bungarotoxin receptor subtypes. Mol. Pharmacol. 47, 164-171. 

The well-studied nicotinic acetylcholine receptors of vertebrates usually consist of two a and three non-a subunits, but a9 forms a heteromer with alO with a stoichiometry of two a9 and three alO subunits when expressed in Xenopus oocytes [8]. Also, a7, a8, and a9 subunits can form functional homomers in the oocyte expression system [9-11], The cation-permeable ion channels of nAChRs open in response to binding of ACh. Most neonicotinoids are agonists of native... 

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