{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:29:37Z","timestamp":1777858177976,"version":"3.51.4"},"reference-count":55,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n                    The antipsychotic efficacy of aripiprazole is not generally associated with extrapyramidal symptoms, cardiovascular effects, sedation or elevations in serum prolactin that characterize typical or atypical antipsychotics. The aim of this study was to clarify the mechanism of action of aripiprazole that underlies its favourable clinical profiles. The preclinical efficacy and side-effect profiles of aripiprazole were evaluated usingseveral pharmaco-behavioural test systems in mice and rats, both in vivo and ex vivo, and compared with those of other conventional and atypical antipsychotics. Each of the antipsychotics induced catalepsy and inhibited apomorphine-induced stereotypy. The catalepsy liability ratios for these drugs were 6.5 for aripiprazole, 4.7 for both olanzapine and risperidone. The ptosis liability ratios for aripiprazole, olanzapine and risperidone were 14, 7.2 and 3.3, respectively. Aripiprazole slightly increased DOPA accumulation in the forebrain of reserpinised mice, reduced 5-HTP accumulation at the highest dose and exhibited a weaker inhibition of 5-methoxy-N,N-dimethyl-tryptamine-induced head twitches. Aripiprazole did not inhibit physostigmine- or norepinephrine-induced lethality in rats. In conclusion, aripiprazole shows a favourable preclinical efficacy and side-effect profile compared to a typical antipsychotics. This profile may result from its high affinity partialagonist activity at D\n                    <jats:sub>2<\/jats:sub>\n                    and 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptors and its antagonism of 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    receptors.\n                  <\/jats:p>","DOI":"10.1177\/026988110401800308","type":"journal-article","created":{"date-parts":[[2004,9,6]],"date-time":"2004-09-06T10:29:15Z","timestamp":1094466555000},"page":"375-383","source":"Crossref","is-referenced-by-count":105,"title":["Mechanism of Action of Aripiprazole Predicts Clinical Efficacy and a                 Favourable Side-Effect Profile"],"prefix":"10.1177","volume":"18","author":[{"given":"Tsuyoshi","family":"Hirose","sequence":"first","affiliation":[{"name":"Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd,                         Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasufumi","family":"Uwahodo","sequence":"additional","affiliation":[{"name":"Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd,                         Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakiko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Aripiprazole Project, Product Planning and Management Group, Otsuka                         Pharmaceutical Co., Ltd, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Miwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuro","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Second Institute of New Drug Discovery, Otsuka Pharmaceutical Co., Ltd,                         Tokushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin D.","family":"Burris","sequence":"additional","affiliation":[{"name":"Palatin Technologies, Cranbury, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Anthony","family":"Altar","sequence":"additional","affiliation":[{"name":"Psychiatric Genomics, Inc., Gaithersburg, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshitaka","family":"Nabeshima","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine, Department of                         Neuropsychopharmacology and Hospital Pharmacy, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2004,9,1]]},"reference":[{"key":"atypb1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1176\/ajp.155.6.761","volume":"155","author":"Abi-Dargham A","year":"1998","journal-title":"Am J Psychiatry"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(86)90181-4"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15419.x"},{"key":"atypb4","first-page":"171","volume":"252","author":"Ashby C R Jr","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200161010-00011"},{"key":"atypb6","doi-asserted-by":"publisher","DOI":"10.3109\/10673229709030552"},{"key":"atypb7","first-page":"1173","volume":"33","author":"Bourin M","year":"1983","journal-title":"Arzneimittelforschung"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(01)01256-2"},{"issue":"1","key":"atypb9","first-page":"S129","volume":"3","author":"Burris K D","year":"2000","journal-title":"Int J Neuropsychopharmacol"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.033175"},{"issue":"8","key":"atypb11","first-page":"20","volume":"61","author":"Conley R R","year":"2000","journal-title":"J Clin Psychiatry"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(73)90138-6"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1007\/BF00436162"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(78)91077-6"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111134598"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1990.tb16877.x"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200216020-00001"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(81)90448-3"},{"key":"atypb19","doi-asserted-by":"publisher","DOI":"10.1007\/BF02246184"},{"key":"atypb20","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-7660"},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n0109"},{"key":"atypb22","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01532-7"},{"key":"atypb23","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v63n0903"},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.153.4.466"},{"key":"atypb25","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.52.1.503"},{"key":"atypb26","first-page":"803","volume":"253","author":"Kelland M D","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"atypb27","first-page":"340","volume":"229","author":"Kenakin T P","year":"1984","journal-title":"J Pharmacol Exp Ther"},{"key":"atypb28","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1166(200112)16:1+<::AID-GPS571>3.0.CO;2-5"},{"key":"atypb29","first-page":"329","volume":"274","author":"Kikuchi T","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"atypb30","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(98)00099-2"},{"issue":"1","key":"atypb31","first-page":"S186","volume":"5","author":"Lieberman J","year":"2002","journal-title":"Int J Neuropsychopharmacol"},{"key":"atypb32","first-page":"434","volume":"93","author":"Loew E R","year":"1984","journal-title":"J Pharmacol Exp Ther"},{"key":"atypb33","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.1.2.305"},{"issue":"1","key":"atypb34","first-page":"S176","volume":"5","author":"McQuade RD","year":"2002","journal-title":"Int J Neuropsychopharm 2002"},{"key":"atypb35","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(03)00050-1"},{"key":"atypb36","volume-title":"Burger\u2019s medicinal chemistry and drug discovery","author":"Martin A","year":"2002","edition":"6"},{"key":"atypb37","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(86)90675-8"},{"key":"atypb38","first-page":"592","volume":"31","author":"Meller E","year":"1987","journal-title":"Mol Pharmacol"},{"key":"atypb39","first-page":"587","volume":"43","author":"Meltzer H Y","year":"1991","journal-title":"Pharmacol Rev"},{"key":"atypb40","first-page":"1356","volume":"286","author":"Millan M J","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"atypb41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1976.tb06961.x"},{"key":"atypb42","doi-asserted-by":"publisher","DOI":"10.1007\/BF00502456"},{"key":"atypb43","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(97)88746-9"},{"key":"atypb44","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.60.7.681"},{"key":"atypb45","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050972"},{"key":"atypb46","first-page":"1279","volume":"20","author":"Puech A J","year":"1981","journal-title":"Neuropharmacology"},{"key":"atypb47","first-page":"153","volume":"13","author":"Qi J H","year":"1992","journal-title":"Zhongguo Yao Li Xue Bao"},{"key":"atypb48","doi-asserted-by":"publisher","DOI":"10.2165\/00023210-200115070-00004"},{"key":"atypb49","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00026-X"},{"key":"atypb50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.14.7673"},{"key":"atypb51","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00057-3"},{"key":"atypb52","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(99)00394-2"},{"key":"atypb53","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(94)90152-X"},{"key":"atypb54","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1176\/jnp.6.4.419","volume":"6","author":"Weinberger D R","year":"1994","journal-title":"J Neuropsychiatry Clin Neurosci"},{"key":"atypb55","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(88)90493-6"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/026988110401800308","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/026988110401800308","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:09:00Z","timestamp":1777507740000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/026988110401800308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,9]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2004,9]]}},"alternative-id":["10.1177\/026988110401800308"],"URL":"https:\/\/doi.org\/10.1177\/026988110401800308","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,9]]}}}