Introduction to the Special Issue “Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence” and a Summary of Patents Targeting other Neurotransmitter Systems

Abstract

This paper introduces the Special Section: Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence and provides a summary of patents targeting neurotransmitter systems not covered in the other four chapters. The World Health Organization notes that alcoholic-type drinking results in 2.5 million deaths per year, and these deaths occur to a disproportionately greater extent among adolescents and young adults. Developing a pharmacological treatment targeting alcohol abuse and dependence is complicated by (a) the heterogeneous nature of the disease(s), (b) alcohol affecting multiple neurotransmitter and neuromodulator systems, and (c) alcohol affecting multiple organ systems which in turn influence the function of the central nervous system. Presently, the USA Federal Drug Administration has approved three pharmacotherapies for alcoholism: disulfiram, naltrexone, and acamprosate. This chapter provides a summary of the following systems, which are not covered in the accompanying chapters; alcohol and acetaldehyde metabolism, opioid, glycinergic, GABA-A, neurosteroid, dopaminergic, serotonergic, and endocannabinoid, as well as patents targeting these systems for the treatment of alcoholism. Finally, an overview is presented on the use of pharmacogenetics and pharmacogenomics in tailoring treatments for certain subpopulations of alcoholics, which is expected to continue in the future.

Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

“…As another example, the UChB, and possibly the UChA, rat line would be ideal for assessing manipulations of the Aldh2 system with compound(s) such as those described by Arolfo et al (2009) and Rezvani et al (2012; also see Bell et al, 2012). This stems from the substantial work examining the alcohol and aldehyde dehydrogenase systems of these rat lines, with genetic alterations in the Aldh2 system playing a prominent role in their divergent ethanol intakes (Quintanilla et al, 2006).…”

“…However, as noted by Johnson (2005, 2010) and Litten et al (2012), complex neuropsychiatric disorders generally require a polypharmacy approach in treatment and there is no reason to expect alcoholism, or drug addiction, to be any different. As a caveat, this conjecture is borne out by the fact that over 75% of the patents granted, between 2000 and 2010, for the treatment of alcoholism world-wide include compounds targeting multiple neurotransmitter, neurohormonal, neuromodulator or enzymatic systems (Bell et al, 2012). It is noteworthy that Rezvani et al (2000)) have conducted a study examining the effects of an intraperitoneally administered cocktail containing naltrexone (6 mg/kg), fluoxetine (3 mg/kg) and a TRH analog (TA-0910, 0.6 mg/kg) on ethanol intake in P, HAD (replicate line not stated) and Fawn Hooded rats.…”

Adolescent alcohol and nicotine exposure alters the adult response to alcohol use

“…Selective breeding for high ethanol intake has produced multiple rat lines that voluntarily consume pharmacologically relevant levels of ethanol under 24 h free-access drinking conditions [e.g., alcohol-preferring (P) and Alko Alcohol (AA)] [c.f. 43 , 44 ]. Such lines have been utilized as a powerful tool to examine the influence of genetic background contributing to the behavioral and neurobiological components of AUDs.…”

Instruments of Personalized Assessment of the Effectiveness of Antipsychotic Therapy: Neurotransmission Receptors on Peripheral Blood Lymphocytes

“…Однако, при введении их в широкую клиническую практику, они оказывались эффективными далеко не для всех пациентов вероятно из-за неоднородности нейрохимических процессов, лежащих в основе развития психических нарушений. Разработка эффективного фармакологического лечения усложняется целым комплексом причин: клиническая гетерогенность; полигенная природа наследования, вклад большого числа генов в риск развития заболевания; изменение генетической пенетрантности, ни у всех носителей аллельных вариантов генов, ассоциированных с риском развития, происходит формирование патологии; эпистатические эффекты; большое количество фенокопий; широкий спектр нейротрансмиттерных систем вовлеченных в патогенезе психических расстройств; нарушение других систем, которые в свою очередь, влияют на функционирование центральной нервной системы [2]. Поэтому, в связи со сложностью и многофакторностью патологии организм каждого человека реагирует индивидуально и проведение какой-то единой стратегии в настоящее время зарекомендовало себя как малоэффективный подход в лечении.…”