167 research outputs found
The novel mu-opioid antagonist, GSK1521498, reduces ethanol consumption in C57BL/6J mice.
RATIONALE
Using the drinking-in-the-dark (DID) model, we compared the effects of a novel mu-opioid receptor antagonist, GSK1521498, with naltrexone, a licensed treatment of alcohol dependence, on ethanol consumption in mice.
OBJECTIVE
We test the ability of GSK1521498 to reduce alcohol consumption and compare its intrinsic efficacy to that of naltrexone by comparing the two drugs at doses matched for equivalent receptor occupancy.
METHODS
Thirty-six C57BL/6J mice were tested in a DID procedure. In 2-day cycles, animals experienced one baseline, injection-free session, and one test session when they received two injections, one of test drug and one placebo. All animals received GSK1521498 (0, 0.1, 1 and 3Â mg/kg, i.p., 30Â min pre-treatment) and naltrexone (0, 0.1, 1 and 3Â mg/kg, s.c. 10Â min pre-treatment) in a cross-over design. Receptor occupancies following the same doses were determined ex vivo in separate groups by autoradiography, using [3H]DAMGO. Binding in the region of interest was measured integrally by computer-assisted microdensitometry and corrected for non-specific binding.
RESULTS
Both GSK1521498 and naltrexone dose-dependently decreased ethanol consumption. When drug doses were matched for 70-75Â % receptor occupancy, GSK1521498 3Â mg/kg, i.p., caused a 2.5-fold greater reduction in alcohol consumption than naltrexone 0.1Â mg/kg, s.c. Both GSK1521498 and naltrexone significantly reduced sucrose consumption at a dose of 1Â mg/kg but not 0.1Â mg/kg. In a test of conditioned taste aversion, GSK1521498 (3Â mg/kg) reduced sucrose consumption 24Â h following exposure to a conditioning injection.
CONCLUSIONS
Both opioid receptor antagonists reduced alcohol consumption but GK1521498 has higher intrinsic efficacy than naltrexone
Differential response to right unilateral ECT in depressed patients: impact of comorbidity and severity of illness [ISRCTN39974945]
BACKGROUND: Recent electroconvulsive therapy (ECT) efficacy studies of right unilateral (RUL) ECT may not apply to real life clinics with a wide range of patients with major depressive episodes. METHODS: The study included two groups of patients. In addition to a homogeneous group of patients with major depression according to DSM-IV criteria with severity of the major depressive episode > 16 scores on 17-item Hamilton Rating Scale for Depression (HDRS) (Group 1, n = 16), we included a heterogeneous group of patients with less severe major depressive episodes or with a variety of comorbid conditions (Group 2, n = 24). We randomly assigned the patients to an RUL ECT treatment dosed at 5 or 2.5 times seizure threshold with an intent-to-treat design. The outcomes measured blindly were HDRS, number of treatments, and Mini-Mental State Examination (MMSE). The patients were considered to have responded to treatment if the improvement in HDRS score was at least 60% and they had a total score of less than ten. RESULTS: The Group 2 patients responded poorer (8% vs. 63%), and had more often simultaneous worsening in their MMSE scores than Group 1 patients. The differences in the outcomes between the two different doses of RUL ECT treatment were not statistically significant. CONCLUSIONS: ECT effectiveness seems to be lower in real-life heterogeneous patient groups than in homogeneous patient samples used in experimental efficacy trials
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