{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:34:54Z","timestamp":1773308094106,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,1,16]],"date-time":"2012-01-16T00:00:00Z","timestamp":1326672000000},"content-version":"vor","delay-in-days":3121,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:p><jats:bold>Objectives.<\/jats:bold> To study the efficacy and safety of 4\u2010aminopyridine (4\u2010AP), and to document sensorimotor changes after discontinuation of the drug in patients with long\u2010term spinal cord injury.<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Randomized, double\u2010blind, placebo\u2010controlled trial.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> Clinical research unit.<\/jats:p><jats:p><jats:bold>Patients.<\/jats:bold> Twenty\u2010seven patients with long\u2010term spinal cord injury.<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> Patients were randomized to receive either oral 4\u2010AP 5 mg\/day, which was increased by 5 mg\/week to a maximum dosage of 30 mg\/day, or placebo for 12 weeks. They switched to the opposite treatment for the next 12 weeks.<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> Twenty\u2010five patients finished the study. The results from the first 12 weeks were used to test efficacy. Positive gains in motor function, sensation, and independence occurred more frequently in patients receiving 4\u2010AP (69%) than those receiving placebo (46%). Significant functional improvement was also noted in those treated with 4\u2010AP (\u03c7<jats:sup>2<\/jats:sup>, p=0.042). When each evaluation scale was considered separately, significant improvement was seen only in motor function (4\u2010AP 92% vs placebo 46%, Fisher exact test, p=0.03). Persistent effects of the drug were assessed at week 24 in the group that initially received 4\u2010AP. A persistent, significant 4\u2010AP effect was observed in evaluations of sensation and independence (67% and 83% of patients, respectively; Wilcoxon signed rank test, p=0.032 and 0.042, respectively). Fourteen (56%) patients had 26 adverse reactions. One moderate adverse reaction\u2014posterior tibial artery vasospasm\u2014and 25 mild adverse reactions, such as dry mouth, dizziness, nausea, gastritis, oral and peripheral paresthesia, resolved adequately. Six (24%) patients experienced transitory alterations of enzyme levels (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and creatine kinase) and thrombocytopenia.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> Patients who received 4\u2010AP showed significant improvement in motor function, and a persistent effect on sensation and independent function occurred. The drug is safe; however, after starting 4\u2010AP therapy, patients must be carefully monitored for the possible occurrence of peripheral vasospasm.<\/jats:p>","DOI":"10.1592\/phco.23.7.823.32731","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T12:11:03Z","timestamp":1084450263000},"page":"823-834","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Efficacy and Safety of 4\u2010Aminopyridine in Patients with Long\u2010Term Spinal Cord Injury: A Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial"],"prefix":"10.1002","volume":"23","author":[{"given":"Israel","family":"Grijalva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Gu\u00edzar\u2010Sahag\u00fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilberto","family":"Castaneda\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Mino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9ctor","family":"Maldonado\u2010Juli\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guadalupe","family":"Vidal\u2010Cant\u00fa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Ibarra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Serra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermelinda","family":"Salgado\u2010Ceballos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Arenas\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,16]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005173222001"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002517-200006000-00001"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1998.15.837"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004150170111"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/cns.1985.2.299"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(86)90025-4"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01252-3"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/283570a0"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(87)90014-1"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(89)90126-3"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1991.8.103"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1993.10.19"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(96)00477-0"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6706"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)01184-6"},{"key":"e_1_2_1_17_2","first-page":"75","article-title":"Observations on the pathology of human spinal cord injury: a review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination","volume":"59","author":"Bunge R.P.","year":"1993","journal-title":"Adv Neurol"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(83)90150-1"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(77)90176-5"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.1.171"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00545-7"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1993.10.1"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sc.1993.40"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1994.11.433"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1997.14.135"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/10790268.1998.11719527"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.19.9.713.31540"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100559"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1089\/089771501316919120"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100432"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.sc.3100504"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1977213247"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1053\/apmr.2001.19780"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1097\/00045391-200201000-00007"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1177\/014107689909201005"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2000.02179.x"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197906213002508"},{"key":"e_1_2_1_38_2","first-page":"1114","article-title":"Gabapentin in partial epilepsy: UK gabapentin study group","volume":"333","year":"1990","journal-title":"Lancet"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.309.6947.86"},{"key":"e_1_2_1_40_2","first-page":"215","article-title":"Neurochemical and neuroreceptor imaging with PET in Parkinson's disease","volume":"86","author":"Stoessl A.J.","year":"2001","journal-title":"Adv Neurol"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-99-6-843"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004290050109"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.1.236"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-199503000-00004"},{"key":"e_1_2_1_45_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002060-199903000-00002"},{"key":"e_1_2_1_46_2","first-page":"466","article-title":"Gastric emptying is impaired in patients with spinal cord injury","volume":"90","author":"Segal J.L.","year":"1995","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90099-X"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00386249"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(96)81861-3"},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.31.3.265"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-199306000-00002"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410320203"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1997.tb03051.x"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.23.7.823.32731","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.23.7.823.32731","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:40:23Z","timestamp":1761054023000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.23.7.823.32731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,7]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2003,7]]}},"alternative-id":["10.1592\/phco.23.7.823.32731"],"URL":"https:\/\/doi.org\/10.1592\/phco.23.7.823.32731","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,7]]},"assertion":[{"value":"2012-01-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}