Preclinical pharmacology of the alpha4beta2 nAChR partial agonist varenicline related to effects on reward, mood and cognition.
The pharmacological properties and pharmacokinetic profile of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline provide an advantageous combination of free brain levels and functional potencies at the target receptor that for a large part explain its efficacy as a smoking cessation aid. Since alpha4beta2 and other nAChR subtypes play important roles in mediating central processes that control reward, mood, cognition and attention, there is interest in examining the effects of selective nAChR ligands such as varenicline in preclinical animal models that assess these behaviors. Here we describe results from studies on varenicline's effects in animal models of addiction, depression, cognition and attention and discuss these in the context of recently published preclinical and preliminary clinical studies that collected data on varenicline's effects on mood, cognition and alcohol abuse disorder. Taken together, the preclinical and the limited clinical data show beneficial effects of varenicline, but further clinical studies are needed to evaluate whether the preclinical effects observed in animal models are translatable to the clinic.
Rollema
Hans
H
Department of Neuroscience Biology, Pfizer Global Research and Development, Groton, CT 06340, USA. hans.rollema@pfizer.com
Hajós
Mihály
M
Seymour
Patricia A
PA
Kozak
Rouba
R
Majchrzak
Mark J
MJ
Guanowsky
Victor
V
Horner
Weldon E
WE
Chapin
Doug S
DS
Hoffmann
William E
WE
Johnson
David E
DE
McLean
Stafford
S
Freeman
Jody
J
Williams
Kathryn E
KE
D000339:Affect / Q000187:drug effects*; D000428:Alcohol Drinking / Q000188:drug therapy / Q000523:psychology; D000818:Animals; D001288:Attention / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy / Q000523:psychology; D054333:Drug Partial Agonism; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D012201:Reward; D014029:Tobacco Use Disorder / Q000188:drug therapy / Q000523:psychology; D000068580:Varenicline
D001552:Benzazepines; D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D011810:Quinoxalines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000068580:Varenicline