Therapeutic applications of 2,5-disubstituted-pyridyl nicotinic ligands

OVERVIEW

Georgetown University and Duke University researchers discovered a potential drug compound treatment that utilizes 2,5-disubstituted-pyridyl nicotinic desensitizer ligands with high affinity and selectivity for α4β2 nicotinic acetylcholine receptors (nAChRs). Such ligands could be used to treat a wide range of neurological and other disorders, including addiction, chemical substance abuse, alcoholism, tobacco abuse, and hypothermia.

BACKGROUND

nAChRs are critical for the initiation and perpetuation of numerous physiological functions and pathological processes. The pharmacological effects of nicotinic drugs and positive reinforcement of nicotine self-administration are mediated mainly through the α4β2 nAChR subtype. Therefore, drug therapies that provide potent and selective desensitization of these receptors could lead to more effective treatments for conditions involving nAChRs.

Benefit

• Small molecules selectively desensitize the α4β2 nAChR subtype with high receptor binding affinity.
• New class of nAChR ligands that show strong in vivo
  effects in animal models, including analgesia, reduction in nicotine self-administration, reduction in alcohol intake, antidepressant-like activity, and reversal of attentional impairment.
• May have a better adverse effect profile than those of other nicotinic ligands.

Market Application

Potential treatment or prevention method for treating chemical substance abuse, alcoholism, and numerous other pathologies that involve nAChRs including Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive-compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism, trichotillomania, and hypothermia.

Publications

• Issued US Divisional Patent No. US9993465B2
• Issued US Utility Patent No. US9303017B2 (04/05/2016)
• Chemistry and pharmacological studies of 3-alkoxy-2,5-disubstituted-pyridinyl compounds as novel selective α4β2 nicotinic acetylcholine receptor ligands that reduce alcohol intake in rats (DOI: 10.1021/jm4000374) (link: https://pubs.acs.org/doi/10.1021/jm4000374)