{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T22:27:34Z","timestamp":1758925654668},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":4848,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1991,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent evidence in vitro has suggested that neuronal injury observed in the acquired immunodeficiency syndrome dementia complex may depend, at least in part, on toxic effects of the human immunodeficiency virus type 1 envelope protein, gp120. This laboratory previously reported that members of the dihydropyridine class of calcium channel antagonists, nimodipine and nifedipine, greatly attenuate the rise in intracellular calcium engendered by gp120 and prevent subsequent neuronal injury. The relatively low (nanomolar) concentrations of dihydropyridines that were effective suggested that their action might be exerted at the level of the L\u2010type of voltage\u2010dependent calcium channels. In the present study, I tested members of the three other major classes of Ca<jats:sup>2+<\/jats:sup> channel antagonist drugs to determine if they too could prevent neurotoxicity induced by gp120. At the maximal dose that did not cause neuronal damage in and of itself, a diphenylalkylamine piperazine derivative (flunarizine, 10 \u03bcM) was the most effective, a phenylalkylamine (verapamil, 100 \u03bcM) was possibly effective, whereas a benzothiazepine (diltiazem, 1 \u03bcM) was ineffectual in protecting rat retinal ganglion cells from gp120\u2010induced toxicity in vitro. To explain these results, previous work has shown that the various classes of Ca<jats:sup>2+<\/jats:sup> channel antagonists may exhibit differential potency in blocking voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup> current in neurons, with dihydropyridines and flunarizine being the most potent at neuronal calcium channels. Moreover, these channels on mammalian central neurons are relatively insensitive to agents such as verapamil and diltiazem compared with other cell types like muscle. The low micromolar concentrations necessary for potency of flunarizine is in keeping with that predicted by binding and electrophysiological studies for block of voltage\u2010dependent calcium channels. Other mechanisms of neuroprotection by flunarizine from gp120, however, cannot be totally excluded.<\/jats:p>","DOI":"10.1002\/ana.410300121","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T12:01:12Z","timestamp":1104580872000},"page":"110-114","source":"Crossref","is-referenced-by-count":56,"title":["Calcium channel antagonists and human immunodeficiency virus coat protein\u2013mediated neuronal injury"],"prefix":"10.1002","volume":"30","author":[{"given":"Stuart A.","family":"Lipton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3277272"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-111-5-400"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294228"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/335639a0"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2326646"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.40.11.1757"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90162-6"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210402"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6143400"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016497"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3014647"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2983428"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/335445a0"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.18.7023"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.17.6556"},{"key":"e_1_2_1_17_2","first-page":"321","article-title":"Calcium antagonism and calcium entry blockers","volume":"38","author":"Godfraind T","year":"1986","journal-title":"Pharmacol Rev"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016864"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.12.4538"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2433765"},{"key":"e_1_2_1_21_2","volume-title":"Advances in pharmacology","author":"Lipton SA","year":"1991"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(90)90040-F"},{"key":"e_1_2_1_23_2","first-page":"289","article-title":"AIDS virus coat protein sensitizes neurons to NMDA receptor\u2010mediated toxicity","volume":"16","author":"Lipton SA","year":"1990","journal-title":"Soc Neurosci Abstr"},{"key":"e_1_2_1_24_2","doi-asserted-by":"crossref","unstructured":"LiptonSA SucherNJ KaiserPK DreyerEB. 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