AbstractThis review aimed to clarify whether antimanic agents used in Japan are superior to placebo for the treatment of acute mania, based on reports of randomized controlled trials (RCTs) conducted in Japan and other East Asian countries. A literature search was conducted using the MEDLINE, PubMed, and Ichushi databases from their dates of inception to July 31, 2021, for studies written in English or Japanese with a primary diagnosis of bipolar I disorder, comparing any of the following active drugs to treat acute mania in adults: aripiprazole, carbamazepine, chlorpromazine, haloperidol, lithium, olanzapine, sultopride, timiperone, and zotepine. A random‐effects network meta‐analysis was performed within a frequentist framework. The quality of each included study was evaluated using the revised Cochrane risk‐of‐bias tool for randomized trials. The outcomes adopted were the response rate for efficacy and dropout rate for tolerability during 3 weeks from baseline. Eleven RCTs, totaling 1148 participants, were reviewed. The pooled odds ratio (OR) (±95% confidence interval [CI]) was calculated. Timiperone (OR = 4.53, CI 1.09–18.80), sultopride (OR = 3.76, CI 1.08–13.05), and aripiprazole (OR = 1.99, CI 1.22–3.24) were significantly more effective than placebo. Olanzapine (OR = 0.51, CI 0.29–0.90) was significantly superior in acceptability to placebo. The results showed no significant differences from placebo for carbamazepine, chlorpromazine, haloperidol, lithium, and olanzapine. These results suggest that noninferiority trials alone cannot always confirm the antimanic drug efficacy and that direct placebo‐controlled trials are necessary to verify the antimanic efficacy of the drugs.

01 Aug 2021·Biological and Pharmaceutical BulletinQ4 · MEDICINE

Inhibitory Effects of Antipsychotics on the Contractile Response to Acetylcholine in Rat Urinary Bladder Smooth Muscles

Q4 · MEDICINE

Article

Author: Hattori, Yume ; Tanaka, Yoshio ; Yamaki, Fumiko ; Iwata, Naoya ; Ikegami, Yohei ; Hamamatsu, Shoko ; Shioda, Nanako ; Yoshio, Takashi ; Yoshioka, Kento ; Obara, Keisuke ; Matsuo, Kazuhiro ; Abe, Yukako ; Matsuoka, Yuka

The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10^-5 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.

01 Jun 2019·Journal of Pharmacological SciencesQ3 · MEDICINE

Characterization of binding of antipsychotics to muscarinic receptors using mouse cerebral cortex

Q3 · MEDICINE

ArticleOA

Author: Horiguchi, Saki ; Yamaki, Fumiko ; Shimada, Toma ; Tanaka, Yoshio ; Matsuo, Kazuhiro ; Ikarashi, Takumi ; Obara, Keisuke ; Yoshio, Takashi

Antipsychotics are often the first-line treatment for behavioral and psychological symptoms of dementia. However, the potential anticholinergic effects of antipsychotics could counteract the therapeutic effects of cholinesterase inhibitors used to treat dementia. We investigated the inhibitory effects of 26 antipsychotics on [N-Methyl-³H]scopolamine specific binding in mouse cerebral cortex. At 10^-5 M, chlorpromazine, levomepromazine, prochlorperazine, timiperone, zotepine, pimozide, blonanserin, olanzapine, quetiapine, and clozapine inhibited [N-Methyl-³H]scopolamine binding by > 45%. Furthermore, the pK_i values of chlorpromazine, levomepromazine, zotepine, olanzapine, and clozapine overlapped with their clinically achievable blood concentrations. Therefore, the anticholinergic properties of these antipsychotics could attenuate the effects of cholinesterase inhibitors.

100 Deals associated with Timiperone

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KEGG	Wiki	ATC	Drug Bank
D02035	Timiperone	N05A	-

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Indication	Country/Location	Organization	Date
Mania	JP	Alfresa Pharma Corp.	12 Jan 1987
Schizophrenia	JP	Alfresa Pharma Corp.	21 Sep 1983

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