Anti-Addiction Drug Ibogaine Inhibits Voltage-Gated Ionic Currents: A Study to Assess the Drug’s Cardiac Ion Channel Profile.
Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug’s cardiac ion channel profile.
Toxicol Appl Pharmacol. 2013 May 22;
Koenig X, Kovar M, Rubi L, Mike AK, Lukacs P, Gawali VS, Todt H, Hilber K, Sandtner W
The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licensed as therapeutic drug, and despite hints that ibogaine may perturb the heart rhythm, this alkaloid is used to treat drug addicts. We have recently reported that ibogaine inhibits human ERG (hERG) potassium channels at concentrations similar to the drugs affinity for several of its known brain targets. Thereby the drug may disturb the heart’s electrophysiology. Here, to assess the drug’s cardiac ion channel profile in more detail, we studied the effects of ibogaine and its congener 18-Methoxycoronaridine (18-MC) on various cardiac voltage-gated ion channels. We confirmed that heterologously expressed hERG currents are reduced by ibogaine in low micromolar concentrations. Moreover, at higher concentrations, the drug also reduced human Nav1.5 sodium and Cav1.2 calcium currents. Ion currents were as well reduced by 18-MC, yet with diminished potency. Unexpectedly, although blocking hERG channels, ibogaine did not prolong the action potential (AP) in guinea pig cardiomyocytes at low micromolar concentrations. Higher concentrations (?10 ?M) even shortened the AP. These findings can be explained by the drug’s calcium channel inhibition, which counteracts the AP-prolonging effect generated by hERG blockade. Implementation of ibogaine’s inhibitory effects on human ion channels in a computer model of a ventricular cardiomyocyte, on the other hand, suggested that ibogaine does prolong the AP in the human heart. We conclude that therapeutic concentrations of ibogaine have the propensity to prolong the QT interval of the electrocardiogram in humans. In some cases this may lead to cardiac arrhythmias. HubMed – addiction
Recipient ineligibility after liver transplantation assessment: a single centre experience.
Can J Surg. 2013 Jun; 56(3): E39-E43
Arya A, Hernandez-Alejandro R, Marotta P, Uhanova J, Chandok N
Candidacy for liver transplantation is determined through standardized evaluation. There are limited data on the frequency and reasons for denial of transplantation after assessment; analysis may shed light on the short-term utility of the assessment. We sought to describe the frequency and reasons for ineligibility for liver transplantation among referred adults.We studied all prospectively followed recipient candidates at a single centre who were deemed unsuitable for liver transplantation after assessment. Inclusion criteria were age 18 years and older and completion of a standard liver transplantation evaluation over a 3-year period. Patients were excluded if they had a history of prior assessment or liver transplantation within the study period. Demographic and baseline clinical data and reasons for recipient ineligibility were recorded.In all, 337 patients underwent their first liver transplantation evaluation during the study period; 166 (49.3%) fulfilled inclusion criteria. The mean age was 55.4 years, and 106 (63.9%) were men. The 3 most common reasons for denial of listing were patient too well (n = 82, 49.4%), medical comorbidities and/or need for medical optimization (n = 43, 25.9%) and need for addiction rehabilitation (n = 28, 16.9%).Ineligibility for transplantation after assessment was common, occurring in nearly half of the cohort. Most denied candidates could be identified with more discriminate screening before the resource-intensive assessment; however, the assessment likely provides unforeseen positive impacts on patient care. HubMed – addiction
Cognitive behavioural therapy for treatmentresistant depression – Authors’ reply.
Lancet. 2013 May 25; 381(9880): 1814-1815
Wiles N, Lewis G, Peters T, Kuyken W, Williams C