General pharmacology最新文献

1. Intravenous venom (0.0625 mg/kg) in the dog caused an immediate increase in coronary blood flow due to a fall in coronary vascular resistance (CVR). 2. Subsequently, total peripheral resistance (TPR) fell causing a significant reduction in aortic blood pressure (ABP). 3. CVR and TPR returned to normal after 20 min but ABP did not recover completely. 4. The failure of ABP to recover was due to decreased stroke volume and cardiac output (CO). 5. Animals died after four doubling doses of venom following irreversible reductions in CO, ABP and coronary flow.

1. A left atrium of guinea pig driven electrically was used as a test organ containing M2-cholinoceptors. 2. Concentration-response curves of carbachol and butyltrimethylammonium, muscarinic full agonists, were progressively inhibited by 10 and 30 min treatments of the atrium with propylbenzilylcholine mustard (PrBCM; 10(-6) M). The 50 min treatment with PrBCM had no further significant inhibitory effect on their curves. 3. The 30 min treatment of the atrium with PrBCM completely inhibited the concentration-response curve of pilocarpine, a partial agonist. In the atrium after the 30 min treatment with PrBCM, pilocarpine shifted the concentration-response curves of the full agonists, suggesting a competitive antagonism. 4. These results suggest an existence of two subtypes of M2-receptors; PrBCM-sensitive and -resistant ones, and that the full agonists inhibit the twitch through an interaction of both the receptors, while the partial agonist produce inhibition through an activation of PrBCM-sensitive ones.

1. The inhibitory actions of two class IB antiarrhythmics, lidocaine and tocainide, on Mg(2+)-dependent ATP hydrolysis by myocardial Na(+)-K(+)-ATPase (EC 3.6.1.3), were tested in guinea-pig heart preparations incubated in media containing 2.5, 5.0 and 10 mM K+. 2. The IC50 values for lidocaine were 2.4 +/- 0.4 mM at 2.5, 4.1 +/- 0.8 mM at 5.0 and 5.3 +/- 0.5 mM at 10 mM K+. The corresponding IC20 values were 0.82 +/- 0.12 mM at 2.5, 1.3 +/- 0.2 mM at 5.0 and 1.7 +/- 0.4 mM at 10.0 mM K+ respectively. Tocainide exerted similar action with IC50 values of 3.1 +/- 0.9 mM at 2.5, 7.6 +/- 1.4 mM at 5.0 and 15.5 +/- 1.6 mM at 10.0 mM K+ and IC20 values of 0.71 +/- 0.19 at 2.5, 2.7 +/- 0.5 mM at 5.0 and 12.3 +/- 1.2 mM at 10.0 mM K+ respectively. 3. Thus, the inhibitory potencies of the drugs on myocardial Na(+)-K(+)-ATPase activity increased significantly with reduction in the K+ concentration. These results demonstrate therefore that the inhibitory actions of both lidocaine and tocainide depend on the K+ concentration of the incubation medium. 4. These findings may be indicative of the importance of K+ in some of the cardiac effects of the antiarrhythmic agents, particularly their tendency to induce or enhance already existing cardiac arrhythmias.

1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.

1. The effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amine (compounds M & E), respectively and diltiazem (D) were examined on the spontaneous and evoked uterine contractions of pregnant rats in vitro. 2. Addition of compound M (75-300 microM), compound E (15-60 microM) or D (100-400 nM) to the uterine tissues, inhibited the spontaneous contractions in a dose-dependent manner. The potency order was D greater than E greater than M. 3. The inhibitions were reversed by elevating the extracellular Ca2+ concentration by 20 mM. The compounds also antagonised CaCl2-evoked contractions. 4. Treatment of rats with either compound during pregnancy days (1-16) did not affect the implantation process and did not induce any teratogenicity. 5. The uterine inhibitory effects of the compounds may be due to blockade of uterine Ca2+ channels.

1. Four different strains of mice were used to study the influence of psychogenetics in opiate tolerance and abstinence. 2. The CD1 strain seemed to be more sensitive to naloxone administration after four days of morphine implantation, because administration of the antagonist induces a number of jumps in the withdrawal phase higher than in the case of the DBA or C3H strains. 3. DBA and C3H mice elicit analgesia before the CD1 strain, whereas the C3H mice lose body weight at a faster rate than the other strains. 4. C57 bl mice died after morphine implantation (100%). 5. These findings are discussed in relation with neurochemical and receptor variations.

1. A clear biphasic response of the enzyme activities as a function of intoxication time due to the topical cutaneous griseofulvin treatment was observed. 2. The initial acute induction of ALA-S activity would be due to depletion of free heme in the regulatory pool caused by cytochrome P 450 destruction. 3. The second induction peak, would be due to less heme formation, secondary to the ferrochelatase inhibition, as expected for the erythropoietic protoporphyria model. 4. The biphasic response of hepatic ALA-D and PBGase activities would be related to ALA-S activity changes and the subsequent augmented available substrates. 5. Endogenous liver porphyrin distribution in cytosolic, mitochondrial and nuclear fractions was investigated. 6. The in vitro biosynthesis of porphyrins confirmed both the biphasic model and the hepatic porphyrins subcellular distribution. 7. Two mechanisms to explain the action of griseofulvin at shorter and longer times of intoxication are proposed.

1. The effects of enkephalins and enkephalinase inhibitors were studied in CA1 area in rat hippocampal slices. 2. The data demonstrate a prevalent involvement of mu opiate receptors in the epileptogenic properties of enkephalins. 3. A potentiation of the mu opiate receptor-mediated epileptogenic response by enkephalinase inhibitors has been shown. 4. The results also show an inability to affect basal CA1 field potentials by inhibition of endogenous endopeptidase.

1. The effect of 10 day treatment with growth hormone (GH) (1 mg/kg body weight/day) and somatostatin (SRIF) (0.25 mg/kg body weight/day) subcutaneously on the activity of 5-HT1 receptors in rat hypothalamic, pituitary and cerebral cortical membrane fractions was studied using [3H]5-HT as radioligand. 2. The administration of GH and SRIF significantly decreased the 5-HT1 binding capacity and affinity in the hypothalamus. 3. In the pituitary the 5-HT1 receptor activity was also significantly decreased after both hormonal applications. 4. In the cerebral cortex the 5-HT1 receptor affinity was significantly decreased and the binding capacity was increased. 5. The results obtained indicate that GH and SRIF decrease 5-HT1 receptor activity. 5-HT1 receptors are possibly involved in the 5-HT controlled GH feedback autoregulation mediated by SRIF.

1. The effects of (+/-)- (+)- and (-)-metoprolol, (+/-)- (+)- and (-)-pindolol, (+/-)-mepindolol and (+/-)-bopindolol on the beta 1-adrenoceptor mediated responses of the rat left atria and the beta 2-adrenoceptor mediated responses of the rat portal vein to isoprenaline have been determined. 2. Racemic and (-)-metoprolol were selective beta 1-adrenoceptor antagonists. (+)-Metoprolol was devoid of beta-adrenoceptor antagonistic activity. 3. Racemic and (-)-pindolol were potent and (+)-pindolol was a modest beta-adrenoceptor antagonist. 4. (+/-)-Mepindolol and (+/-)-bopindolol were apparently competitive antagonists of the isoprenaline beta 1-adrenoceptor mediated responses of the rat left atria but non-competitive antagonists of the isoprenaline beta 2-adrenoceptor mediated responses of the rat portal vein. 5. It is suggested that (+/-)-mepindolol and (+/-)-bopindolol are slowly dissociating beta-adrenoceptor antagonists and the non-competitive antagonism can only be detected on tissues with modest receptor reserves for maximum responses to isoprenaline.