Repurposing drugs for treatment of alcohol use disorder.

Repurposing drugs for the treatment of alcohol dependence involves the use of drugs that were initially developed for other conditions, but have shown promise in reducing alcohol use or preventing relapse. This approach can offer a more cost-effective and time-efficient alternative to developing new drugs from scratch. Currently approved medications for alcohol use disorder (AUD) include acamprosate, disulfiram, naltrexone, nalmefene, baclofen, and sodium oxybate. Acamprosate was developed specifically for AUD, while disulfiram's alcohol-deterrent effects were discovered incidentally. Naltrexone and nalmefene were originally approved for opioids but found secondary applications in AUD. Baclofen and sodium oxybate were repurposed from neurological conditions. Other drugs show promise. Topiramate and zonisamide, anticonvulsants, demonstrate efficacy in reducing alcohol consumption. Another anticonvulsant, gabapentin has been disappointing overall, except in cases involving alcohol withdrawal symptoms. Varenicline, a nicotinic receptor agonist, benefits individuals with less severe AUD or concurrent nicotine use. Ondansetron, a 5-HT3 antagonist, has potential for early-onset AUD, especially when combined with naltrexone. Antipsychotic drugs like aripiprazole and quetiapine have limited efficacy. Further investigation is needed for potential repurposing of α1 adrenergic receptor antagonists prazosin and doxazosin, glucocorticoid receptor antagonist mifepristone, the phosphodiesterase inhibitor Ibudilast, the cysteine prodrug N-acetylcysteine, and the OX1R and OX2R blocker Suvorexant. This review supports repurposing drugs as an effective strategy for expanding treatment options for AUD.

The Persistent Challenge of Developing Addiction Pharmacotherapies.

There are currently effective Food and Drug Administration (FDA)-approved therapies for alcohol, nicotine, and opioid use disorders. This article will review the development of eight compounds used in the treatment of drug addiction with an emphasis on pharmacological mechanisms and the utility of preclinical animal models of addiction in therapeutic development. In contrast to these successes, animal research has identified a number of promising medications for the treatment of psychostimulant use disorder, none of which have proven to be clinically effective. A specific example of an apparently promising pharmacotherapeutic for cocaine that failed clinically will be examined to determine whether this truly represents a challenge to the predictive validity of current models of cocaine addiction. In addition, the development of promising cocaine use disorder therapeutics derived from animal research will be reviewed, with some discussion regarding how preclinical studies might be modified to better inform clinical outcomes.

NeuroHeal Reduces Muscle Atrophy and Modulates Associated Autophagy.

Muscle wasting is an unmet medical need which leads to a reduction of myofiber diameter and a negative impact on the functional performance of daily activities. We previously found that a new neuroprotective drug called NeuroHeal reduced muscle atrophy produced by transient denervation. Aiming to decipher whether NeuroHeal has a direct role in muscle biology, we used herein different models of muscle atrophy: one caused by chronic denervation, another caused by hindlimb immobilization, and lastly, an in vitro model of myotube atrophy with Tumor Necrosis Factor-α (TNFα). In all these models, we observed that NeuroHeal reduced muscle atrophy and that SIRT1 activation seems to be required for that. The treatment downregulated some critical markers of protein degradation: Muscle Ring Finger 1 (MuRF1), K48 poly-Ub chains, and p62/SQSTM1. Moreover, it seems to restore the autophagy flux associated with denervation. Hence, we envisage a prospective use of NeuroHeal at clinics for different myopathies.

Very Low Frequency of Drug Therapy of Alcohol Dependence in Germany - Analysis of Data of A Statutory Health Insurance.

Acamprosate and naltrexone are medications of proven efficacy in the treatment of alcohol dependence. In order to investigate the prescription of these drugs in outpatient routine treatment in Germany (frequency of prescription, duration, medical specialty of prescribing physician), data of a large statutory health insurance were analyzed. Persons were included who were discharged from inpatient treatment with an alcohol-related disorder among their diagnoses during a one year observation period and with no diagnosed additional substance-related disorder (apart from nicotine- and cannabis-related disorders). Thus 12.958 patients were identified (mainly male, 77.9%; at average 51.4 years [+/-12.7] of age). 44.3% of these patients were treated in a psychiatric hospital, the remaining patients in hospitals of other specialties (e. g. 9.2% in departments of surgery). During an observation period of 6 months after discharge, acamprosate or naltrexone were prescribed at least once to 98 persons (0.76% of 12.958 patients; acamprosate n=80, 0.62%; naltrexone n=18, 0.14%). 16 (0.12%) patients were prescribed acamprosate or naltrexone for more than 3 months. Half of the prescriptions were issued by general practitioners. Possible reasons for this under-prescription are lack of knowledge about the drug treatment of alcohol dependence outside of addiction psychiatry, neglect of biological aspects (including medication) regarding etiology and treatment of substance-related disorders, and stigma of patients with substance-related disorders.

Evolución de pacientes con adicción al alcohol con el uso de acamprosato / Progression of patients with alcohol dependence using acamprosate

Introducción: los efectos del consumo excesivo de bebidas alcohólicas para el individuo, la familia y la sociedad son un problema de salud, convertido en la más trascendente toxicomanía en la actualidad. En el mercado existen tres fármacos que reducen el deseo de beber y son el disulfiram, la naltrexona y el acamprosato. El acamprosato es el medicamento que se propone estudiar, ya que en Cuba no existen referencias anteriores de estudios de la efectividad del acamprosato. Objetivo: valorar la evolución del alcoholismo y su tratamiento con acamprosato. Métodos: se diseñó un Estudio de Utilización de Medicamentos observacional y descriptivo, basado en las consecuencias prácticas del uso del acamprosato en pacientes diagnosticados con adicción al alcohol, con una dosis de dos cápsulas de 33,3 mg diarias por vía oral, durante seis meses de tratamiento, desde septiembre de 2012 a febrero de 2013. Resultados: de 44 pacientes evaluados, el 90,9 por ciento no tuvo recaídas, solamente el 9,1 por ciento de los pacientes tuvo deseos de consumir alcohol al inicio del tratamiento. Un paciente mostró intranquilidad como efecto adverso al acamprosato. La autovaloración de todos los pacientes fue positiva, refiriendo en su totalidad que cambiaron para una persona mejor. El 68,2 por ciento de los pacientes tuvieron una evolución excelente, lo que coincide con otros estudios internacionales con el acamprosato. Conclusiones: el tratamiento con acamprosato es efectivo para la prevención de las recaídas y la reducción del consumo de alcohol en el alcoholismo(AU)

Introduction: the effects of the excessive intake of alcohol beverages for the individual, the family and the society represent a health problem turned into the most transcendental toxicomania at present times. There are three drugs on the market which reduce the desire of drinking and are called disulfiram, naltrexone and acamprosate. The latter is the drug to be studied since there are no previous references in Cuba about effectiveness study of acamprosate. Objective: to assess the progression of alcoholism and its treatment with acamprosate. Methods: adescriptive and observational Study of Drug Use was designed on the basis of the practical consequences of the use of acamprosate in patients diagnosed with alcohol dependence, at a dose of two caplets of 33.3mg to be taken daily for six months from September 2012 to February 2013. Results: of 44 evaluated patients, 90.9 percent had no relapses, just 9.1 percent felt the desire of taking alcohol beverages at the onset of treatment. One patient showed restlessness as adverse effect of the drug. The self-assessment of all the patients was positive, stating that they changed into a better person after treatment. In the group, 68.2 percent had an excellent progress which agrees with other international study on this drug. Conclusions: the treatment with acamprosate is effective for the prevention of relapses and the reduction of alcohol dependence(AU)