The results of our in vivo preclinical studies corroborate those obtained from previously conducted in vitro experiments of bilastine, and provide evidence that bilastine possesses antihistaminic as well as antiallergic properties, with similar potency to cetirizine and superior potency to fexofenadine.

These preclinical studies provide evidence that bilastine has H1- antihistamine activity, with high specificity for H1-receptors, and poor or no affinity for other receptors. Bilastine has also been shown to have anti-inflammatory properties.

New 2-(methoxyphenyl)piperazine derivatives 1 and 2 containing a terminal heteroaryl or cycloalkyl amide fragment were prepared and their 5-HT1A affinities evaluated by radioligand binding assays. The influence of the alkyl chain length or the amide group on affinity was evaluated. A four-carbon chain appears to be optimal when the amide fragment is a heteroaryl group. Derivatives with a cycloalkyl moiety displayed maximum affinity in the two methylene chain series. Electronic distribution within the amide region seems to have an influence on affinity in heteroaryl derivatives. Replacement of the heteroaryl moiety by a cycloalkyl group led to compounds with enhanced affinity. Increasing the lipophilicity of the cycloalkyl derivatives by annelation and/or saturation increased their affinity for the 5-HT1A sites. Compounds with cis-bicyclo[3.3.0]octane (2a, 2c), norbornane (2f, 2g), and norbornene (2h, 2i) groups bind at 5-HT1A sites with 2-10-fold higher affinity than NAN-190. Antagonist activity at alpha 1-adrenergic receptors was evaluated for compounds with high affinity at 5-HT1A sites. Compounds 2a, 2c, 2f, 2g, and 2h strongly bind (Ki = 0.12-0.63 nM) at 5-HT1A receptors and are devoid of antagonist activity at alpha 1-adrenergic receptors.

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