TRPM8 Ion Channel Ligands for New Therapeutic Applications and as Probes to Study Menthol Pharmacology.

TRPM8 Ion Channel Ligands for New Therapeutic Applications and as Probes to Study Menthol Pharmacology.

Filed under: Addiction Rehab

Life Sci. 2012 Nov 15;
Journigan VB, Zaveri NT

Since the discovery of the TRPM8 gene in 2001, the TRPM8 ion channel, better known as the ‘cold receptor’ has been the target of a significant effort from the pharmaceutical industry to produce small-molecule agonists and antagonists of this receptor for various therapeutic applications ranging from cancer and urological disorders to the treatment of cold hypersensitivity and pain. Recently, a number of clinical studies have implicated the natural ligand of TRPM8, l-(-)-menthol, as facilitating and maintaining cigarette smoking behavior, possibly through its counter-irritant effects. However, a pharmacological link between menthol’s action via TRPM8 and nicotine addiction has not been yet been investigated. This review gives an overview of reported small-molecule TRPM8 agonists and antagonists and discusses their efficacy in models of various disease states. These compounds may be useful pharmacological tools to investigate the effect of menthol on nicotine addiction.
HubMed – addiction

 

New Insights on Neurobiological Mechanisms underlying Alcohol Addiction.

Filed under: Addiction Rehab

Neuropharmacology. 2012 Nov 13;
Cui C, Noronha A, Morikawa H, Alvarez VA, Stuber GD, Szumlinski KK, Kash TL, Roberto M, Wilcox MV

Alcohol dependence/addiction is mediated by complex neural mechanisms that involve multiple brain circuits and neuroadaptive changes in a variety of neurotransmitter and neuropeptide systems. Although recent studies have provided substantial information on the neurobiological mechanisms that drive alcohol drinking behavior, significant challenges remain in understanding how alcohol-induced neuroadaptations occur and how different neurocircuits and pathways cross-talk. This review article highlights recent progress in understanding neural mechanisms of alcohol addiction from the perspectives of the development and maintenance of alcohol dependence. It provides insights on cross talks of different mechanisms and reviews the latest studies on metaplasticity, structural plasticity, interface of reward and stress pathways, and cross-talk of different neural signaling systems involved in binge-like drinking and alcohol dependence.
HubMed – addiction

 

Independent versus substance-induced major depressive disorders in first-admission patients with substance use disorders: An exploratory study.

Filed under: Addiction Rehab

J Affect Disord. 2012 Nov 13;
Langås AM, Malt UF, Opjordsmoen S

BACKGROUND: Clinical differences between independent and substance-induced (S-I) major depressive disorders (MDDs) in patients with substance use disorders (SUDs) are insufficiently studied. METHODS: The catchment area sample consisted of 42 SUD patients with independent and/or S-I MDD (bipolar disorders excluded), admitted consecutively to addiction clinics or psychiatry departments (inpatient or outpatient) with no previous treatment history from specialized services. Assessments included the Psychiatric Research Interview for Substance and Mental Disorders (PRISM), the Structured Clinical Interview for DSM-IV, Axis II, Personality Disorders (SCID-II), the Inventory of Depressive Symptoms (IDS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Symptom Check List, 90 questions, revised (SCL-90-R). RESULTS: Of the 42 SUD patients, 48% had independent MDD episode(s) only, 24% had S-I MDD episode(s) only, and 28% had both independent and S-I MDD episodes. Insomnia, psychomotor agitation, concentration and decision problems, melancholic features, higher total MDD symptom count, longer time being depressed, higher mean score on the Montgomery-Asberg Depression Rating Scale, and shorter duration of SUDs characterized independent MDDs. LIMITATIONS: Small sample size with risk of type II error. CONCLUSIONS: Independent MDDs were more severe and had different qualities compared with S-I MDDs, suggesting important treatment implications. Longitudinal studies including larger samples and carefully addressing the association between SUD subtypes and MDD subtypes are needed to substantiate our findings.
HubMed – addiction

 

Review article: towards a considered and ethical approach to organ support in critically-ill patients with cirrhosis.

Filed under: Addiction Rehab

Aliment Pharmacol Ther. 2012 Nov 16;
Berry PA, Thomson SJ, Rahman TM, Ala A

BACKGROUND: Increasing numbers of patients are being admitted to hospital with decompensated chronic liver disease in the UK. A significant proportion will develop complicating extra-hepatic organ dysfunction, but the selection of those who should be admitted to intensive care is complex and challenging. Alcohol-related liver disease also presents complex ethical dilemmas. AIM: To review recent survival analyses and explore differences in secondary and tertiary care; to highlight strengths and weaknesses of prognostic models, therapeutic advances and shifts in prognostic expectation. We also aim to explore the ethical challenges presented by addiction and self-injury in an area of limited resource. METHODS: We searched PubMed for articles discussing ‘cirrhosis’, ‘prognosis’, ‘critical illness’, ‘organ failure’, ‘renal failure’, ‘alcohol’, ‘ethics’ and ‘addiction’. We also explored particular ethical dilemmas encountered by the authors and colleagues. RESULTS: Prognosis has improved in many cirrhotic complications and historically poor outcomes in tertiary care may reflect a more complex patient cohort. Previously ‘untreatable’ complications are now being managed successfully. Estimates of survival are more accurate after a 48-h period of supportive care. Physicians are not best placed to make judgments with regard to deservingness, moral responsibility, rationing and access to organ support in cases of acute deterioration related to alcoholism, and the case for denying support must be made on purely medical grounds. CONCLUSIONS: An early, aggressive approach to organ support is justified. Further discussions between hepatologists and critical care physicians are required to determine acceptable burden-to-benefit ratios for prolonged intensive care support in young alcoholic patients.
HubMed – addiction

 


 

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