[en] The effects of deuteration on the metabolism and activity of nitroglycerin and imipramine has been investigated in the rat. Deuteration of nitroglycerin produced no significant isotope effect on biological denitration and the two forms were pharmacologically identical. Deuteration of imipramine produced a significant kinetic isotope effect, although this was quite small having a magnitude of approx. 1.33. The isotope effect occurred on the N - demethylation step, and no isotope effect was observed for aromatic hydroxylation. Although a significant slowing of biological half-life occurred, there were no changes in the pharmacological properties of deuteroimipramine from imipramine. The general pharmacokinetic properties of each drug have also been studied and, in the case of nitroglycerin, extensive in vitro investigations have been conducted to elucidate the tissue site, subcellular site and nature of the enzyme(s) responsible for denitration. (U.K.)

[en] The effect of pre-expose to hexachlorobenzene (HCB). toxaphene (TX) or DDT (100 ppm in the diet for 8 days in each case) on the excretory function of the bile was investigated using isolated perfused rat-liver preparations obtained from treated and control animals. Hepatic uptake, metabolism and biliary excretion of [¹⁴C]imipramine (IMP) was examined in these studies. Biliary excretion of endogenously formed metabolites of IMP was enhanced by pre-exposure to HCB, by 18% after 2 hr of perfusion. Pre-exposure to DDT and TX resulted in a decrease in biliary excretion of endogenously formed metabolites of IMP. HCB-induced enhancement of biliary excretion was not associated with either the bile flow or the rate at which IMP was metabolized. However, DDT and TX pretreatments elicited a decrease in the rate of IMP metabolism as well as in bile production, observations commensurate with the decrease in biliary excretion. Biliary excretion of exogenously provided, readily excretable metabolites of IMP was decreased by pre-exposure to HCB as well as to DDT or TX. In the light of these observations an alternative mechanism for HCB-induced modification of biliary excretion has been proposed. This mechanism assumes the existence of a 'synthetic' and a 'post-synthetic' pool of metabolites, the biliary removal of metabolites from each of these pools being subject to modification by HCB. An enhancement of the biliary excretion of IMP metabolites from the 'synthetic' pool and impairment of removal from the 'post-synthetic' pool would be consistent with the above results. (author)

[en] The chronic effects of antidepressant treatment on striatal dopaminergic (DA) and muscarinic cholinergic (mACh) receptors of the rat brain have been examined comparatively in this study using ³H-spiroperidol (³H-SPD) and ³H-quinuclidinyl benzilate (³H-QNB) as the respective radioactive ligands. Imipramine and desipramine were used as prototype antidepressants. Although a single administration of imipramine or desipramine did not affect each receptor sensitivity, chronic treatment with each drug caused a supersensitivity of mACh receptor subsequent to DA receptor subsensitivity. Furthermore, it has been suggested that anti-mACh properties of imipramine or desipramine may not necessarily be related to the manifestation of mACh receptor supersensitivity and that sustained DA receptor subsensitivity may play some role in the alterations of mACh receptor sensitivity

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[en] The authors used the recent tritium-sensitive film method of quantitative autoradiography to localize in rat brain high-affinity binding sites for nitroimipramine (NI), a long-lasting inhibitor of serotonin (5-HT) transport in platelets. The distribution of NI binding sites in rat brain closely parallels the location of 5-HT terminals. There are high concentrations of binding sites in the dorsal and medial raphe nuclei, the basal portion of the mammilary nuclei, the medial forebrain bundle, the olfactory tubercule and the posterior basal nucleus of the amygdala. The association of [₃H]NI binding sites with regions having a high content of 5-HT supports the notion that the high-affinity binding site for [₃H]NI corresponds to some aspect of the presynaptic uptake site for 5-HT. (Auth.)

[en] Levonantradol is a cannabis derivative. Cannabinoid anti-emetics are being assessed in cancer chemotherapy but have been little used in radiotherapy to date. A pilot study and randomised trial compared the anti-emetic effect of a standard drug (Chlorpromazine 25 mg) with Levonantradol at two doses (0.5 and 0.75 mg) in patients receiving palliative single fraction radiotherapy to sites likely to cause nausea and vomiting. Most patients were out-patients. Both drugs were well tolerated. The frequency of vomiting was similar in all three groups in both the pilot study and randomised trial. (author)

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[en] A technique is described for producing pulse-like effects in [³H]thymidine autoradiography in chick embryos. This procedure involves combining thymidine with reserpine, which temporarily inhibits thymidine incorporation. The concept is to introduce thymidine, allow time for its incorporation, then introduce reserpine, so that subsequent uptake is inhibited, and a relatively discrete label will appear in cells generated at the time of thymidine administration. The best results occurred when thymidine was administered 12 h prior to reserpine, or when the two were introduced simultaneously. A dose of 0.004 mg of reserpine produced the suppression, but had no deleterious effects, in terms of embryonic survival or in long-lasting changes in cell numbers, as reflected by cell counts in the trochlear nucleus, a population which was undergoing proliferation at the time of reserpine injection. Thus, this technique appears to hold considerable promise for improving the precision of the autoradiography procedure in avian embryos. (Auth.)

No abstract available