Background:

Varenicline Hydrochloride (CP 526555 hydrochloride) is a high affinity, selective α4β2 nicotine acetylcholine receptor (nAChR) partial agonist and full α7 nAChR agonist[1][2][3]. Varenicline Hydrochloride is also a potent partial agonist of α6β2 nAChR in striatum of rats with a Ki value of 0.12 nM[4].

Varenicline (0.5-2 mg/kg/day; subcutaneous injection; twice daily; for 14 days; male Wistar rats) treatment shows a comparable significantly higher DRD2/3 availability in the ventral striatum of approximately 11%, while only the rats treated with 1 and 2 mg/kg/day dose shows significantly higher DRD2/3 availability in the dorsal striatum by 12.5% and 13.2%, respectively. Varenicline induces dose-dependent and sustained increases in striatal DRD2/3 in rats, particularly in the ventral striatum[1].

参考文献:
[1]. Crunelle CL, et al. Dose-dependent and sustained effects of varenicline on dopamine D2/3 receptor availability in rats. Eur Neuropsychopharmacol. 2011 Feb;21(2):205-10.
[2]. Kikkawa H, et al. Single- and multiple-dose pharmacokinetics of the selective nicotinic receptor partial agonist, varenicline, in healthy Japanese adult smokers. J Clin Pharmacol. 2011 Apr;51(4):527-37.
[3]. Pachas GN, Cather C, Pratt SA et al. Varenicline for Smoking Cessation in Schizophrenia: Safety and Effectiveness in a 12-Week, Open-Label Trial. J Dual Diagn. 2012;8(2):117-125.
[4]. Bordia T, Hrachova M, Chin M et al. Varenicline Is a Potent Partial Agonist at α6β2* Nicotinic Acetylcholine Receptors in Rat and Monkey Striatum. J Pharmacol Exp Ther. 2012 Aug;342(2):327-34.