Targeting Opioid and Neurokinin-1 Receptors to Treat Alcoholism

F.      D. Rodriguez; R.      Covenas

doi:10.2174/092986711797200444

Abstract

Alcoholism is a multifarious and ongoing disease tightly related to the amount of alcohol ingested, the drinking pattern, the history of alcohol drinking and the individual features, such as some genetic traits. Worldwide alcohol is the necessary cause of approximately 60 diseases and causes circa 2.5 million deaths every year. Studies show that alcohol interacts with brain neurotransmission in a complex manner. Dopaminergic, GABAergic, serotonergic, cholinergic and glutamatergic systems are all key participants in the action of ethanol on the brain. Furthermore, several neuropeptides, such as endogenous opioid peptides, substance P, corticotropin-releasing hormone, or the appetite-regulating peptides (eg., neuropeptide Y, ghrelin or orexin) also play a role in alcohol drinking. Treatment of alcohol use disorders (AUD) is based on the application of combined approaches, including pharmacological intervention directed to different molecular targets. Results, however, are variable, not always satisfactory, and not applicable to all stages and pathologies or to all patients. New strategies focused on the control of neuropeptide performance in the brain are being explored and may be an advance in the therapy of alcoholism. The application of treatments ad personam represents a challenge that currently stimulates research in different realms, including epidemiology, psychology, chemistry, biochemistry, cell biology and pharmacology. In this review the potential value and application of ligands that modulate the function of opioid and neurokinin-1 receptors in alcoholism therapy is analyzed.

Keywords: Alcoholism, neurokinin-1 receptor (NK1R) antagonists, NK1R, opioids, reward, substance P, neurotransmission, Dopaminergic, GABAergic, serotonergic