3 Adrenergic receptor antagonist pharmacokinetics

Risperidone (11) was also included among a a 1-adrenergic receptor antagonists to study a quantitative structure-activity relationship (99BMC2437). A pharmacophore model for atypical antipsychotics, including 11, was established (00MI41). An increased plasma level of 11 and 9-hydroxyrisperidone (12) was observed in combination with paroxetine (01 MI 13). The effect of vanlafaxine on the pharmacokinetics of 11 was reported (99MI13). 

Compared to the reference compound SCH 38393 they exhibit similar or more potent activities, high selectivity over D2-D4 receptors and improved in vivo pharmacokinetics. The optimization of the hydrogen bond donating capacity of various heterocycles allowed the identification of several potent D1/D5 antagonists with high selectivity D2-D4, a2a adrenergic receptors, and the 5-HT transporter keeping at the same time excellent pharmacokinetic profiles. 

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