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

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 alpha-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 alpha-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 H1-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.

Histamine and H3 receptor-dependent mechanisms regulate ethanol stimulation and conditioned place preference in mice

“…This finding is in agreement with the hypothesis of inhibitory effect of histamine on reward, based on enhancement of hypothalamic self-stimulation by the lesions of the TMN (Wagner et al 1993;Huston et al 1997) and on potentiation of the rewarding effects of opioids by H1 receptor antagonists (Shannon and Su 1982;Suzuki et al 1995) and amphetamines (Masukawa et al 1993). These findings have received some criticism, since the lesions of TMN affect several other neurotransmitter systems in addition to histamine, and most of the H1 receptor antagonists display a high affinity for the dopamine transporter (Oishi et al 1994). Thus, using a genetic approach to deplete histamine, we show here that histamine indeed seems to inhibit the development of reward.…”

Clemizole Hydrochloride Is a Novel and Potent Inhibitor of Transient Receptor Potential Channel TRPC5

“…It was developed in the 1950s to treat allergic reactions and various dermatological diseases (Zierz and Greither, 1952;Jacques and Fuchs, 1960). Besides its antihistaminergic action, clemizole inhibits monoamine reuptake in the brain (Oishi et al, 1994) and blocks human ether-a-go-go related gene (hERG) channels at a concentration of 10 mM (data obtained from http://pubchem.ncbi.nlm.nih.gov). Nowadays, clemizole is not marketed as a single-agent antihistamine anymore.…”

Comparative anatomy of the histaminergic and other aminergic systems in zebrafish (Danio rerio)

“…Histamine inhibits release of noradrenaline in cortex of rats, guinea pigs, and humans by means of H 3 receptors (Schliker et al, 1989(Schliker et al, , 1999Timm et al, 1998). Histamine induces increased release and turnover of noradrenaline in mouse and rat brain by activation of H 1 receptor (Shishido et al, 1991;Bealer, 1993;Oishi et al, 1994;Fleckenstein et al, 1994a,b). Histamine has also been found to inhibit noradrenaline release from nerve terminals by means of H 1 receptors in the paraventricular nucleus of rats and, thus, suppressing feeding behavior (Kurose and Terashima, 1999).…”