Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile

Tsuyoshi Hirose, Yasufumi Uwahodo, Sakiko Yamada, Takashi Miwa, Tetsuro Kikuchi, Hisashi Kitagawa, Kevin D. Burris, C. Anthony Altar, Toshitaka Nabeshima

研究成果: Article

125 引用 (Scopus)

抜粋

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 using several 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 atypical antipsychotics. This profile may result from its high affinity partial agonist activity at D 2 and 5-HT1A receptors and its antagonism of 5-HT 2A receptors.

元の言語English
ページ(範囲)375-383
ページ数9
ジャーナルJournal of Psychopharmacology
18
発行部数3
DOI
出版物ステータスPublished - 01-09-2004
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

これを引用

Hirose, T., Uwahodo, Y., Yamada, S., Miwa, T., Kikuchi, T., Kitagawa, H., Burris, K. D., Altar, C. A., & Nabeshima, T. (2004). Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile. Journal of Psychopharmacology, 18(3), 375-383. https://doi.org/10.1177/026988110401800308