{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T16:13:21Z","timestamp":1762100001074},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2003,1,9]],"date-time":"2003-01-09T00:00:00Z","timestamp":1042070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2003,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several analogs of the acetylcholine precursor molecule choline have been widely studied as potential false cholinergic neurotransmitters with the therapeutic goal of using them to limit cholinergic neurotransmission. More recently, choline itself has been shown to act as a full, if low potency, agonist at the \u03b17 subtype of the nicotinic acetylcholine receptor. This pharmacological property has been associated with the ability of nicotine and other related \u03b17 receptor agonists to offer neuroprotection in a variety of experimental models. We confirm here that choline offers a significant degree of protection against the cytotoxicity induced by growth factor deprivation in differentiated PC\u201012 cells. Choline\u2010induced cytoprotection (\u223c1 mM) was about 3 orders of magnitude less potent than that for nicotine (EC<jats:sub>50<\/jats:sub> = 0.7 \u03bcM). Choline also exhibited only about 40% of the full cytoprotective effect of nicotine. Ethyl substitution for choline's N\u2010methyl groups did not result in a significant improvement over choline as a cytoprotective agent. In contrast, pyrrolidinecholine exhibited much greater potency (EC<jats:sub>50<\/jats:sub> = 20 \u03bcM) and increased efficacy (about 55% of nicotine's effect) than choline. Like choline and nicotine, pyrrolidinecholine fully displaced [<jats:sup>125<\/jats:sup>I]\u03b1\u2010bungarotoxin binding (K<jats:sub>i<\/jats:sub> = 33 \u03bcM) and chronic exposure to the analog increased cell surface binding sites. The cytoprotective effects of the analog were completely inhibited by coincubation with methyllycaconitine (MLA), a selective \u03b17\u2010nicotinic receptor antagonist. These findings are consistent with the possibility that the choline structure may serve as a template for the development of novel agents with both \u03b17\u2010nicotinic agonist activity and potential neuroprotective ability, as many of these compounds, including pyrrolidinecholine, are transported along with choline into the central nervous system. Synapse 47:262\u2013269, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/syn.10176","type":"journal-article","created":{"date-parts":[[2003,1,22]],"date-time":"2003-01-22T22:17:36Z","timestamp":1043273856000},"page":"262-269","source":"Crossref","is-referenced-by-count":29,"title":["Relative levels of cytoprotection produced by analogs of choline and the role of \u03b17\u2010nicotinic acetylcholine receptors"],"prefix":"10.1002","volume":"47","author":[{"given":"Ramamohana R.","family":"Jonnala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"John H.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvin V.","family":"Terry Jr.","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Warren","family":"Beach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A.","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerry J.","family":"Buccafusco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,1,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91678-0"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1997.tb01702.x"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00006-6"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002093-199501002-00009"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(82)90207-5"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(88)90037-8"},{"key":"e_1_2_1_8_1","first-page":"86","article-title":"Comparative studies of substrates and inhibitors of choline transport and choline acetyltransferase","volume":"192","author":"Barker LA","year":"1975","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1981.tb01649.x"},{"key":"e_1_2_1_10_1","first-page":"57","volume-title":"Neurotransmitter receptor binding","author":"Bennett JP","year":"1978"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1980.tb07864.x"},{"key":"e_1_2_1_12_1","article-title":"SIB\u20101553A ((\u00b1)2\u2010[2\u2010(4\u2010hydroxyphenyl) thioethyl]\u20101\u2010methypyrolidine), a novel cholinergic ion channel agonist with cognitive\u2010enhancing properties. 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