A steric approach for the design of antihistamines with low muscarinic receptor antagonism

  title={A steric approach for the design of antihistamines with low muscarinic receptor antagonism},
  author={M. -Q. Zhang and Krzysztof Walczyński and Henk Timmerman},
  journal={Inflammation Research},
For years, the clinical utility of histamine Hi-receptor antagonists (also known as antihistamines) has been hampered by two major side effects: (1) sedation, most likely resulting from blockade of histamine Hi-receptors in the central nervous system (CNS), and (2) muscarinic receptor antagonism, causing dry mouth, blurred vision, tachycardia and nervousness. The CNS depression of antihistamines can be avoided by designing drugs incapable of crossing the blood-brain barrier, e.g. by introducing… Expand
Antimuscarinic actions of antihistamines on the heart.
The data presented here show that one of the newest antihistamines, desloratadine, and a first generation drug, diphenhydramine, are both competitive inhibitors of muscarinic receptor mediated slowing of the heart as measured using a Langendorff preparation. Expand


Structure-activity relationships within a series of analogues of the histamine H1-antagonist terfenadine
Abstract A number of terfenadine derivatives including terfenadine enantiomers were synthesized and tested for histamine H 1 -receptor affinity. No significant differences in H 1 activity were foundExpand
(+)- and (-)-3-Methoxycyproheptadine. A comparative evaluation of the antiserotonin, antihistaminic, anticholinergic, and orexigenic properties with cyproheptadine.
As a peripheral serotonin antagonist, (+/-)-4 was found to be one-half as potent as cyproheptadine (1b) but the peripheral anticholinergic and antihistaminic activities as well as the orexigenic property of (+/--4 are less than those of 1b. Expand
Muscarinic acetylcholine receptor subtypes in smooth muscle.
In this review, Richard Eglen and colleagues discuss recent data concerning the possible role(s) of muscarinic receptor subtypes in smooth muscle and appraise the pharmacological methods for dissecting the function of mus carinic receptorSubtypes in tissues co-expressing multiple receptors. Expand
Computerassisted analysis of the possible binding sites of HI-antagonists
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