Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain (original) (raw)

Abstract

To compare in vivo effects of eleven compounds of different classes of histamine H1-receptor antagonists (alcoholamines: diphenhydramine, carbinoxamine, and clemastine; ethylenediamines: mepyramine, tripelennamine, and clemizole; alkylamines: triprolidine and chlorpheniramine; piperazines: meclizine and homochlorcyclizine; phenothiazines: promethazine) on neuronal uptake of dopamine (DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT), the effects on the turnover of these monoamines were examined in the mouse brain, based on the a-methyl-p-tyrosine-induced depletion of DA and NA or probenecid-induced accumulation of 5-hydroxyindoleacetic acid. The DA turnover was reduced remarkably by diphenhydramine, tripelennamine, and promethazine, and also significantly by chlorpheniramine, mepyramine, clemizole, and homochlorcyclizine, at doses used in the ordinary animal experiments. The 5-HT turnover was reduced markedly by mepyramine, tripelennamine, and chlorpheniramine. In contrast, the NA turnover was increased by promethazine and homochlorcyclizine, possibly due to their antagonistic effects on α-adrenoceptors. These results suggest that (1) the degree of inhibition of the uptake of DA and 5-HT by histamine H1-receptor antagonists is considerably different, (2) most Ht-antagonists have little influence on NA uptake and some compounds enhance NA release, and that (3) carbinoxamine, clemastine, triprolidine, and meclizine have comparatively weak influences on monoamine metabolism. These effects on brain monoamine systems may be related to some central actions of histamine H1-receptor antagonists, such as an addiction to these compounds combined with opioids.

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Author notes

1. Ryozo Oishi
   Present address: Department of Hospital Pharmacy, Okayama University Medical School, 700, Okayama, Japan

Authors and Affiliations

1. Department of Pharmacology, Okayama University Medical School, 2-5-1, 700, Shikata-cho, Okayama, Japan
   Ryozo Oishi, Setsu Shishido, Motoo Yamori & Kiyomi Saeki

Authors

1. Ryozo Oishi
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2. Setsu Shishido
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3. Motoo Yamori
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4. Kiyomi Saeki
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Correspondence to: R. Oishi at the above address

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Oishi, R., Shishido, S., Yamori, M. et al. Comparison of the effects of eleven histamine H1-receptor antagonists on monoamine turnover in the mouse brain.Naunyn-Schmiedeberg's Arch Pharmacol 349, 140–144 (1994). https://doi.org/10.1007/BF00169830

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• Received: 11 June 1993
• Accepted: 13 October 1993
• Issue Date: February 1994
• DOI: https://doi.org/10.1007/BF00169830

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