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961.
Cocaethylene, a psychoactive metabolite resulting from combined ethanol/cocaine consumption, is of interest because its psychostimulant properties may partially underlie combined cocaine/ethanol use, and because it has the potential for use as a probe of drug reward mechanisms due to its enhanced selectivity at monoamine uptake sites compared to cocaine. To determine the relative systemic bioavailabilities of cocaine and cocaethylene, sequential plasma samples were obtained from awake rats following drug administration. Following intravenous administration of 3 µmol/kg (molar equivalent of 1 mg/kg cocaine-HCl), both drugs achieved similar time courses and areas under the plasma concentration versus time curve. In contrast, intraperitoneal administration of 44 µmol/kg (molar equivalent of 15 mg/kg cocaine HCl) showed peak plasma levels, and the area under the plasma concentration vs time curve for cocaine to be approximately twice that for cocaethylene. Comparison of dose corrected areas under the curve of the two routes of administration for each drug indicated that relative systemic bioavailability of cocaethylene following intraperitoneal administration is only 58% that of cocaine. In addition, the elimination of both cocaine and cocaethylene was found to be slower following intraperitoneal administration compared to the intravenous route. The implications of these results are discussed with respect to the relative potency of these two compounds, as inferred from behavioral, drug reward, and lethality studies. Also, the differences noted will need to be taken into account when making mechanistic interpretations from comparative drug reward studies. 相似文献
962.
The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed. 相似文献
963.
Zh. A. Mamyrbekova S. A. Soldatova V. I. Abelentsev T. I. Solov'eva V. N. Guryshev A. T. Soldatenkov 《Pharmaceutical Chemistry Journal》1994,28(3):198-202
Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 3, pp. 48–51, March, 1994. 相似文献
964.
V. I. Nifontov N. P. Bel'skaya E. A. Shtokareva 《Pharmaceutical Chemistry Journal》1994,28(10):687-706
Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 10, pp. 4–18, October 1994. 相似文献
965.
M. M. Rasulov I. G. Kuznetsov A. G. Zabozlaev M. G. Voronkov 《Pharmaceutical Chemistry Journal》1994,28(7):441-445
Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 7, pp. 3–6, July, 1994. 相似文献
966.
T. V. Golovko N. I. Mikerova L. M. Alekseeva G. A. Bogdanova V. A. Parshin V. V. Asnina R. B. Parimbetova V. G. Granik 《Pharmaceutical Chemistry Journal》1994,28(4):236-242
Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 28, No. 4, pp. 22–26, April, 1994. 相似文献
967.
Pharmaceutical Chemistry Journal - 相似文献
968.
969.
Haiyung Cheng Jules I. Schwartz Charles Lin Raju D. Amin James R. Seibold Kenneth C. Lasseter David L. Ebel Dominick J. Tocco J. Douglas Rogers 《Biopharmaceutics & drug disposition》1994,15(5):409-418
MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD4-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg 14C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative. 相似文献
970.
Contact angles of substances used for internal tamponade in retinal detachment surgery 总被引:4,自引:0,他引:4
I. M. Fawcett R. L. Williams D. Wong 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》1994,232(7):438-444
In order to ascertain the tamponade effect of air and silicone oil we examined the contact angles subtended by ex vivo human retina, Teflon and Perspex to find a suitable experimental material which would mimic the surface properties of the retina at a three-phase interface. Using the captive bubble technique to measure the contact angle, it was found that air subtended a larger contact angle (38.8°) with the retina than did silicone oil (18.2°). On coating the Perspex surface with protein (PCP), it was observed that the surface properties were modified such that PCP subtended contact angles with air (43.0°) and silicone oil (16.4°) similar to those subtended by ex vivo human retina. Using PCP as an experimental material that mimics ex vivo human retina, spherical chambers were employed in order to examine qualitatively and to quantify the arc of contact obtained with air and silicone oil. It was found that air gave a greater arc of contact for the same percentage fill than silicone oil. 相似文献