Antimuscarinic effects of antihistamines : Quantitative evaluation by receptor-binding assay.

Abstract

Abstract-Quantitative evaluation of antimuscarinic effects of antihistamines (H1 and H2-receptor antagonists) was carried out using a receptor-binding assay. The inhibition constants (K; values) of twenty seven H1-receptor antagonists, one related antidepressant and three H2-receptor antagonists at Hi-receptors and muscarinic receptors in the bovine cerebral cortex were determined. All the H2 receptor antagonists examined showed very low affinity for the muscarinic receptors. On the other hand, some Hl-receptor antagonists (mequitazine, cyproheptazine, clemastine, diphenylpyraline, promethazine, homochlorcyclizine and alimemazine) had high affinity for the muscarinic receptors (K;=5.0-38 nM). Another group of H, -receptor antagonists (mepyramine, terfenadine, metapyrilen, azelastine, hydroxyzine and meclizine) had low affinity for the muscarinic receptors (K;=3,600 30,000 nM). Thus, a broad range of antimuscarinic potencies among the anti histamines was demonstrated. These results should provide helpful information with regard to the clinical and experimental use of antihistamines.

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial

“…Clemastine fumarate is well known to have antagonistic effects on a wide variety of membrane-bound G-protein-coupled neuro transmitter receptors. 38 Furthermore, animal experiments indicate that at our selected dose we only achieved partial saturation of the target muscarinic receptor (data not shown; dose adjusted). Non-selective drugs with anticholinergic effects have been suggested to have anticognitive effects in uncontrolled studies in patients with multiple sclerosis.…”

Sedation and histamine H1‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

“…Published studies on dimethindene are limited, though the racemic compound has less potent anticholinoceptor than antihistamine receptor activity, both centrally and peripherally, and does not antagonize cardiovascular effects of noradrenaline, adrenaline and acetylcholine in the dog. However, doses of dimethindene which inhibit histamine-induced gastro-intestinal motility also reduce the response to 5-HT (Barrett et al, 1961;Kubo et al, 1987).…”

“…Marked differences between the activity of the enantiomers have also been observed in rabbit aorta (O'Neill & Patil, 1975 (Hill et al, 1978;Tran et al, 1978;Chang et al, 1979;Quach et al, 1980). It is of interest that there are no marked species differences in stereoselectivity ratios, even though the ability of chlorpheniramine to displace the labelled ligand varies (Chang et al, 1979). Dimethindene is a potent H, antihistamine, with activity similar to or greater than that of (+)-chlorpheniramine in a number of tests of histamine receptor function (Barrett et al, 1961) and in receptor binding studies (Tran et al, 1978;Kubo et al, 1987). Its stereoselectivity with respect to H1 sites is less well documented, but (-)-dimethindene is between 20 and 100 times more potent than the (+)-isomer in blocking the response to histamine receptor activation in various guineapig tissue preparations (Borchard et al, 1985).…”

Case Files of the Medical Toxicology Fellowship at Drexel University

“…DPH and the other ethanolamine antihistamines are potent competitive antagonists at muscarinic acetylcholine receptors [10]. DPH also acts as an antagonist at serotonin receptors, although the clinical relevance of this interaction is unclear [11].…”