WAY-100635 is a potent and selective 5-hydroxytryptamine 1A (5-HT1A) receptor antagonist with an IC50 of 0.91 nM and Ki of 0.39 nM, exhibiting pIC50 values of 8.9 and 6.6 for 5-HT1A and α1-adrenergic receptors, respectively. Additionally, WAY-100635 acts as a potent agonist of the dopamine D4 receptor [1] [2] [3].

The functional properties and binding affinities of WAY-100635 were assessed in HEK 293 cells stably expressing dopamine D 2L or D 4.4 receptors [1]. The compound exhibits binding affinities of 940, 370, and 16 nM for D 2L, D 3, and D 4.2 receptors, respectively. Saturation analysis revealed a dissociation constant (Kd) of [3 H]WAY-100635 at D 4.2 receptors of 2.4 nM. WAY-100635 acts as a potent agonist in HEK-D 4.4 cells with an effective concentration 50 (EC50) of 9.7 nM and shows high affinity for the D 4.4 receptor at 3.3 nM [1].

Administration of WAY-100635 (1 mg/kg; subcutaneous injection) to male Sprague-Dawley rats counteracts the decrease in severity of withdrawal symptoms observed following Rhodiola rosea treatment in nicotine-dependent rats [2]. This pharmacokinetic study utilized an animal model consisting of male Sprague-Dawley rats weighing 220-240 g, treated with a dosage of 1 mg/kg via subcutaneous injection. The outcomes included a reduction in total withdrawal scores, alongside an increase in immobility time and burying behavior.