Therapeutic applications of phenyl-substituted nicotinic ligands

OVERVIEW

Georgetown University and Duke University researchers discovered a potential drug treatment that utilizes phenyl-substituted 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, and tobacco abuse.

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

• Method to selectively desensitize the α4β2 nAChR subtype.
• A new class of nAChR ligands shows 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.

Market Application

Potential treatment or prevention method for treating addiction, pain, obesity, schizophrenia, epilepsy, mania and manic depression, anxiety, Alzheimer's disease, learning deficit, cognition deficit, attention deficit, memory loss, Lewy Body Dementia, Attention Deficit Hyperactivity Disorder (ADHD), Parkinson's disease, Huntington's disease, Tourette's syndrome, amyotrophic lateral sclerosis, inflammation, stroke, spinal cord injury, dyskinesias, obsessive-compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, autism, mutism, trichotillomania, hypothermia, and disorders of sleep.

Publications

• Issued US Patent No.: US9346784B2 (5/24/2016)
• Issued US Patent No.: US9994548B2 (6/12/2018)
• Design, Synthesis and Discovery of Picomolar Selective α4β2 Nicotinic Acetylcholine Receptor Ligands (DOI: https://doi.org/10.1021/jm4008455) (link: https://pubs.acs.org/doi/10.1021/jm4008455)