Abstract
Abuse of and addiction to psychostimulants such as cocaine or amphetamines remain a significant societal burden, and attempts at successfully developing effective treatments for substance use disorders involving psychostimulants have been disappointingly unsuccessful to date. In addition, most pharmacologically based approaches to treating psychostimulant use disorders have largely focused on targeting monoaminergic or amino acid neurotransmission, with little emphasis being placed on neuropeptide systems. One such neuropeptide system that has received little attention is the tachykinin family of peptides and their corresponding neurokinin (NK) receptor subtypes designated NK1, NK2, and NK3. Tachykinins and their receptors are widely expressed in numerous cell types in the periphery and central nervous system, and in the latter, regulate fundamental processes such as nociception, reward, motivation, affect, and stress responses. In recent years, various small molecule brain penetrant NK1 antagonists have been developed which appear to be beneficial and well tolerated in patients undergoing treatment for chemotherapy-induced and post-operative nausea and vomiting. The purpose of this review is to summarize the small body of preclinical and clinical studies that suggest NK1 antagonists may be of potential use in the treatment of substance use disorders involving psychostimulants. Additional topics of discussion will be the importance of full receptor occupancy and known species differences in NK1 receptor ligand binding, which represent significant obstacles to utilizing standard rodent models of psychostimulant addiction for future screening of potentially efficacious NK1 antagonists.
Keywords: Addiction, alcohol, cocaine, neurokinin-1 receptor, opiate, substance P, substance use disorder, tachykinin.
CNS & Neurological Disorders - Drug Targets
Title:Neurokinin-1 (NK1) receptor antagonists as possible therapeutics for psychostimulant use disorders
Volume: 14 Issue: 6
Author(s): Michael F. Olive
Affiliation:
Keywords: Addiction, alcohol, cocaine, neurokinin-1 receptor, opiate, substance P, substance use disorder, tachykinin.
Abstract: Abuse of and addiction to psychostimulants such as cocaine or amphetamines remain a significant societal burden, and attempts at successfully developing effective treatments for substance use disorders involving psychostimulants have been disappointingly unsuccessful to date. In addition, most pharmacologically based approaches to treating psychostimulant use disorders have largely focused on targeting monoaminergic or amino acid neurotransmission, with little emphasis being placed on neuropeptide systems. One such neuropeptide system that has received little attention is the tachykinin family of peptides and their corresponding neurokinin (NK) receptor subtypes designated NK1, NK2, and NK3. Tachykinins and their receptors are widely expressed in numerous cell types in the periphery and central nervous system, and in the latter, regulate fundamental processes such as nociception, reward, motivation, affect, and stress responses. In recent years, various small molecule brain penetrant NK1 antagonists have been developed which appear to be beneficial and well tolerated in patients undergoing treatment for chemotherapy-induced and post-operative nausea and vomiting. The purpose of this review is to summarize the small body of preclinical and clinical studies that suggest NK1 antagonists may be of potential use in the treatment of substance use disorders involving psychostimulants. Additional topics of discussion will be the importance of full receptor occupancy and known species differences in NK1 receptor ligand binding, which represent significant obstacles to utilizing standard rodent models of psychostimulant addiction for future screening of potentially efficacious NK1 antagonists.
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Cite this article as:
Olive F. Michael, Neurokinin-1 (NK1) receptor antagonists as possible therapeutics for psychostimulant use disorders, CNS & Neurological Disorders - Drug Targets 2015; 14 (6) . https://dx.doi.org/10.2174/1871527314666150529145811
DOI https://dx.doi.org/10.2174/1871527314666150529145811 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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