Acta pharmacologica et toxicologica最新文献

The effect and tolerability of hydrochlorothiazide 12.5 mg and bendroflumethiazide 2.5 mg were compared in 36 previously untreated hypertensives in a double-blind randomized multicenter trial. The results show a significant blood pressure reduction with both hydrochlorothiazide 12.5 mg and bendroflumethiazide 2.5 mg both at month 6 and 12 compared with month 0. Serum potassium was not significantly changed after twelve months of therapy with either of the thiazide compared with month 0. There was no significant difference between hydrochlorothiazide and bendroflumethiazide with respect to the hypotensive effect, the effect on potassium and uric acid in serum, fasting blood glucose, or any other variable studied. Few subjective side effects were reported.

Possible differences between the muscarinic receptors in the guinea pig urinary bladder and those in the ileum and the parotid gland were investigated, using a receptor binding technique. The affinities of 18 antimuscarinic drugs were indirectly derived from the ability to inhibit the receptor-specific binding of the radioligand (-)3H-QNB. The Hill coefficients were close to unity which indicated that the drugs were bound to apparently uniform populations of receptors within each tissue. In contrast to traditional muscarinic antagonists, four drugs - namely, oxybutynine, dicyclomine, benzhexol and pirenzepine - bound with a significantly higher affinity in the parotid gland than in the urinary bladder and ileum. A tendency towards reversed selectivity was found for secoverine. Thus, the present results further support the hypothesis that differences in muscarinic receptors between tissues exist, e.g. smooth muscle compared with parotid gland, which can be detected only by certain antimuscarinic drugs.

A rapid, yet highly reliable, procedure for determination of homovanillic acid (HVA) in plasma is described. After precipitation of proteins with perchloric acid, separation of sample components is directly achieved with high performance liquid chromatography on a reversed-phase column (C8), followed by quantitation based on electrochemical detection. The sensitivity of this method is 0.5 pmol/injection. Detector response is linear from the limit of detection to at least 0.5 nmol/injection. The intra-assay coefficient of variation is 2.2% in the concentration range of 50-150 pmol/ml plasma. The inter-assay coefficient of variation is 6.3%, based on determinations on 30 working days. A comparison of the present method and a specific gas chromatographic-mass spectrometric assay showed good agreement between the two procedures. One chromatographic run requires less than 16 min. for plasma and 10 min. for a standard.

Rats were treated with lithium added to their diet for five weeks (40 mmol LiCl/kg diet). Mean plasma concentration was 0.45 mmol Li+/plasma. The investigation was divided into two sections. I) In an in vivo experiment in which the rats were injected with 32P-orthosphosphate for 20 hours, and with carbamoylcholine for 20 min. prior to their death, the distribution of 32P in the synaptosomal phospholipids, phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and phosphatidylcholine (PC), was investigated. II) An in vitro experiment which was carried out in order to establish the effect of carbamoylcholine on the incorporation of 32P into total phospholipids from extracted synaptosomes. In I) the incorporation of 32P-orthosphosphate into PI from carbamoylcholine-stimulated rats was significantly lower than from unstimulated rats, whereas there was no difference between the incorporation of 32P into PI from synaptosomes from control animals and lithium-treated animals. In II) the incorporation of 32P-orthosphosphate was significantly lower in unstimulated synaptosomes from lithium-treated rats than from control rats, while the increase in the 32P-incorporation after stimulation followed the same pattern with regard to synaptosomes from control rats and lithium-treated rats. The results support the idea of lithium exerting an effect on basal synaptosomal activity but not on stimulated synaptosomal activity.

The effects of certain monovalent (Ag+1 and Li+1), divalent (Hg+2, Cu+2, Zn+2, Co+2, Fe+2, Pb+2, Mn+2, Sn+2, Ni+2, and Se+2) and trivalent (Fe+3, As+3, and Al+3) metals on a mitochondrial preparation of K+-stimulated-p-nitrophenyl phosphatase (K+-PNPPase) from rat brain were studied. Except for salts of Ni+2, Se+2 and Li+1, which irrespective of concentration failed to produce 50% inhibition, all of the metals examined were found to be potent inhibitors of the enzyme with 150 values of 0.24 microM for Ag+1 among the monovalent, 0.70, 30, 37, 38, 47, 60, 62, 490 and 850 microM for Hg+2, Cu+2, Cd+2, Zn+2, Co+2, Fe+2, Pb+2, Mn+2 and Sn+2, respectively, among the divalents and 100, 550 and 870 microM for Fe+3, As+3, and AL+3 respectively, among the trivalents. Salts of silver and mercury were the most toxic for this enzyme. All metals showed concentration dependent inhibition except lithium. The order of their potency was Ag+1 greater than Hg+2 greater than Cu+2 greater than Cd+2 greater than Zn+2 greater than Co+2 greater than Fe+2 greater than Pb+2 greater than Fe+3 greater than Mn+2 greater than As+3 greater than Sn+2 greater than Al+3 greater than Ni+2 greater than Se+2 greater than Li+1.

Isolated hamster lungs were ventilated with smoke from low-, medium-and high-tar cigarettes when 45 nmol of 14C-arachidonic acid was infused into the pulmonary circulation. Most of the infused radioactivity was found in different phospholipid and neutral lipid fractions of the perfused lungs and a smaller amount was found in the nonrecirculating perfusion effluent mainly as metabolites. Cigarette smoke ventilation increased the amount of 14C-arachidonic acid in the triacylglycerols of the perfused lungs but had usually no effect on the amount of radioactivity in diacylglycerols or in different phospholipids. The increased amount of radiolabel in triacylglycerols was significantly greater in the lungs ventilated with smoke from medium-or high-tar cigarettes than in those ventilated with low-tar cigarette smoke. Cigarette smoke ventilation increased the amount of unmetabolized arachidonate in the perfusion effluent and decreased the amount of many metabolites. The present study indicates that low-, medium- and high-tar cigarettes have effects of the fate and metabolism of arachidonic acid in isolated hamster lungs and that the effects of medium- and high-tar cigarettes are more clear that those of low-tar cigarettes when the cigarettes are burned with a constant puff volume and rate.