Inhibitory Effects of Antipsychotics on the Contractile Response to Acetylcholine in Rat Urinary Bladder Smooth Muscles
| Autor: | Yume Hattori, Yohei Ikegami, Yukako Abe, Naoya Iwata, Yoshio Tanaka, Nanako Shioda, Yuka Matsuoka, Kazuhiro Matsuo, Kento Yoshioka, Keisuke Obara, Shoko Hamamatsu, Takashi Yoshio, Fumiko Yamaki |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Dibenzothiepins
Male Urologic Diseases Fluphenazine Aging Chlorpromazine Urinary Bladder Pharmaceutical Science Pharmacology Cholinergic Antagonists Tiapride Quetiapine Fumarate chemistry.chemical_compound Methotrimeprazine medicine Animals Asenapine Rats Wistar Clozapine business.industry Mental Disorders Blonanserin Muscle Smooth General Medicine Acetylcholine chemistry Olanzapine Zotepine Quetiapine Pipamperone business Antipsychotic Agents Muscle Contraction medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 44:1140-1150 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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