Results 1 - 10 of 274
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[en] Introduction: No model exists to describe the disposition and kinetics of inhaled cannabis containing a high THC dose. We aimed to develop a kinetic model providing estimates of the THC serum concentrations after smoking cannabis cigarettes containing high THC doses (up to 69 mg THC). Methods: Twenty-four male non-daily cannabis users smoked cannabis cigarettes containing 29.3 mg, 49.1 mg, and 69.4 mg THC. Blood samples were collected over a period of 0-8 h and serum THC concentrations were measured. A two-compartment open model was fitted on the individual observed data. Results: Large inter-individual variability was observed in the pharmacokinetic parameters. The median pharmacokinetic parameters generated by the model were Cmax = 175 ng/mL, Tmax = 14 min, and AUC0-8h = 8150 ng x min/mL for the 69.4 mg THC dose. Median model results show an almost linear dose response relation for Cmax/Dose = 2.8 x 10-6/mL and AUC0-8h/Dose = 136 x 10-6 min/mL. However, for increasing dose level, there was a clear decreasing trend: Cmax/Dose = 3.4, 2.6 and 2.5 x 10-6/mL and AUC0-8h/Dose = 157, 133 and 117 x 10-6 min/mL for the 29.3, 49.1 and 69.4 mg dose, respectively. Within the restriction of 8 h of observation, the apparent terminal half life of THC was 150 min. Conclusion: The model offers insight into the pharmacokinetics of THC in recreational cannabis users smoking cannabis containing high doses of THC mixed with tobacco. The model is an objective method for providing serum THC concentrations up to 8 h after smoking cannabis with a high THC content (up to 23%).
[en] A radioreceptor assay (RRA) for determining benzodiazepines (BZ) has been developed and applied to toxicological analysis of serum samples from 21 patients with acute BZ overdosage. The method was sensitive (e.g., lorazepam 17 nM, diazepam 41 nM), and specific for pharmacologically active BZ derivatives. The reproducibility of the results was good (intra-assay variation < 8%, inter-assay variation < 10%). Concentrations measured by the RRA showed a good correlation with those obtained by gas-liquid chromatographic analysis of the same samples. The quantitative results represent the sum of one or several parent substances and all biologically active metabolites, in proportion to their receptor binding affinities. (author)
[en] The patent relates to a technique for enabling rapid determination of the concentration of neuroleptic drugs such as the phenthiazines and butyrophenones in body fluids of patients. The method is based on the discovery that a neuroleptic drug contained in the body fluid of a patient will successfully compete with the binding of radioactive dopamine receptor site binders to dopamine receptor sites of dopamine receptor material in such a manner that an accurate determination of neuroleptic drug concentration can readily be made. The invention relates to method of radioassay, to a composition of matter for enabling such assays, and to a test kit for the performance of such assays. (U.K.)
[en] The study was designed to test the hypothesis that a decrease in the responsiveness of somatodendritic 5-HT-1A receptors by co- administration of imipramine could reverse the induction of VCMs and supersensitivity at 5-HT-IA receptors by haloperidol. Rats treated with haloperidol 0.2mg/rat/day for 2 weeks induced VCMs with twitching of facial musculature that increased in a time dependent manner as the treatment continued to 5 weeks. Co administration of imipramine (5mg/kg/m1) attenuated haloperidol-induced VCMs after 2 weeks and completely reversed it after 5 weeks. The intensity of 8-hydroxy -2-di(n-propyleamino)tetraline (8-OH-DPAT)-induced locomotion and forepaw treading were greater in saline+haloperidol injected but not in imipramine+haloperidol injected animals. 8-OH-DPAT induced decreases of 5-HT metabolism were greater in saline+haloperidol injected animals but not in imipramine+haloperidol injected animals. The mechanism involved in reversal/attenuation of haloperidol-induced tardive dyskinesia by imipramine is discussed. (author)
[en] N,N'-Dimethyl 2-naphthaleneethanimidamide monohydrochloride (DL-588) is a potential psychotherapeutic agent for which a sample of carbon-13 labelled material was required for metabolism studies. The sample of 90% 13C enriched DL-588 was prepared starting with 90% 13C enriched potassium cyanide in three steps. 2-(Bromomethyl)naphthalene was treated with the 13C potassium cyanide under phase transfer catalysis. The resulting 13C-2-napthylacetonitrile was converted to the imidate ester hydrochloride under Pinner reaction conditions. This intermediate was treated with excess methylamine in ethanol at 550 to give the title compound in an overall yield of 68%. The effects of 13C labelling on the 1H NMR spectra of the final product and intermediates are discussed. (author)