Peripheral and central H1 histamine receptor occupancy by levocetirizine, a non-sedating antihistamine; a time course study in the guinea pig.

Background And Purpose: The H(1) receptor occupancy (H1RO) in brain is an indicator of central side effects of antihistamines. Here, we determined the kinetics of central and peripheral H1RO by levocetirizine in relation to its brain and plasma concentration, and investigated the role of the blood-brain barrier in any delay in brain H1RO.

Experimental Approach: Concentration-time profiles in plasma and brain were obtained after 0.

Contractile properties of various histaprodifen derivatives in guinea pig isolated ileum and trachea.

We characterized the histamine H(1) receptor agonism of various histaprodifen derivatives in guinea pig isolated ileum and trachea in comparison with histamine. Based on their affinity (calculated pK(A) values for ileum and trachea, respectively), the compounds were ranked as follows: suprahistaprodifen (8.31/8.

Stereoselective pharmacokinetics of cetirizine in the guinea pig: role of protein binding.

Purpose: To characterize the pharmacokinetics of cetirizine enantiomers in the guinea pig including protein binding in both the guinea pig and human plasma.

Methods: Plasma concentrations of cetirizine enantiomers in the guinea pig were determined using a LC-MS/MS method after a short i.v.

Brain distribution of cetirizine enantiomers: comparison of three different tissue-to-plasma partition coefficients: K(p), K(p,u), and K(p,uu).

The objective of this study was to compare the blood-brain barrier (BBB) transport and brain distribution of levo- (R-CZE) and dextrocetirizine (S-CZE). Microdialysis probes, calibrated using retrodialysis by drug, were placed into the frontal cortex and right jugular vein of eight guinea pigs. Racemic CZE (2.

Potent anti-muscarinic activity in a novel series of quinuclidine derivatives.

The synthesis and biological evaluation of a novel family of M(3) muscarinic antagonists are described. A systematic modification of the substituents to a novel alkyne-quinuclidine scaffold yielded original compounds displaying potent in vitro anticholinergic properties.