The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform
Maarten E A Reith - One of the best experts on this subject based on the ideXlab platform.
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cations affect 3h Mazindol and 3h win 35 428 binding to the human dopamine transporter in a similar fashion
Journal of Neurochemistry, 2002Co-Authors: Qun Wu, Maarten E A Reith, Lori L CoffeyAbstract:: The present study addresses the possibility that there are different cocaine-related and Mazindol-related binding domains on the dopamine transporter (DAT) that show differential sensitivity to cations. The effects of Zn2+, Mg2+, Hg2+, Li+, K+, and Na+ were assessed on the binding of [3H]Mazindol and [3H]WIN 35,428 to the human (h) DAT expressed in C6 glioma cells under identical conditions for intact cell and membrane assays. The latter were performed at both 0 and 21 degrees C. Zn2+ (30-100 microM) stimulated binding of both radioligands to membranes, with a relatively smaller effect for [3H]Mazindol; Mg2+ (0.1-100 microM) had no effect; Hg2+ at approximately 3 microM stimulated binding to membranes, with a relatively smaller effect for [3H]Mazindol than [3H]WIN 35,428 at 0 degrees C, and at 30-100 microM inhibited both intact cell and membrane binding; Li+ and K+ substitution (30-100 mM) inhibited binding to membranes more severely than to intact cells; and Na+ substitution was strongly stimulatory. With only a few exceptions, the patterns of ion effects were remarkably similar for both radioligands at both 0 and 21 degrees C, suggesting the involvement of common binding domains on the hDAT impacted similarly by cations. Therefore, if there are different binding domains for WIN 35,428 and Mazindol, these are not affected differentially by the cations studied in the present experiments, except for the stimulatory effect of Zn2+ at 0 and 21 degrees C and Hg2+ at 0 degrees C.
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win 35 428 and Mazindol are mutually exclusive in binding to the cloned human dopamine transporter
Journal of Pharmacology and Experimental Therapeutics, 1997Co-Authors: Cen Xu, Maarten E A ReithAbstract:It has been suggested that cocaine and Mazindol bind to separate sites on the dopamine transporter. In the present study, we address this issue by examining the inhibition by Mazindol of the binding of [3H]WIN 35,428 ([3H]2β-carbomethyoxy-3β-(4-fluorophenyl)-tropane), a phenyltropane analog of cocaine, and the inhibition by WIN 35,428 of [3H]Mazindol binding to the cloned human dopamine transporter expressed in C6 glioma cells. The design involved the construction of inhibition curves at six widely different radioligand levels, enabling the distinction between the nonlinear hyperbolic competition ( i.e. , negative allosteric) model and the competitive ( i.e. , mutually exclusive binding) model. Nonlinear computer curve-fitting analysis indicated no difference in the goodness of fit between the two models; the negative allosteric model indicated an extremely high allosteric constant of ∼ ≥100, which practically equates to the competitive model. The present results suggest that complex interactions reported between cocaine and Mazindol in inhibiting dopamine transport are beyond the level of ligand recognition.
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radiolabeling of dopamine uptake sites in mouse striatum comparison of binding sites for cocaine Mazindol and gbr 12935
Naunyn-schmiedebergs Archives of Pharmacology, 1992Co-Authors: Maarten E A Reith, Gabor SelmeciAbstract:This study addressed the possibility of a unique binding interaction between cocaine and the dopamine transporter as compared with other blockers of dopamine uptake. Cocaine binding sites in a fresh P2 fraction of mouse striatum were labeled with [3H]CFT, a phenyltropane analog of cocaine also known as WIN 35,428, and compared with sites labeled with [3H]Mazindol or [3H]GBR 12935. Under the conditions used, homogeneous binding was observed that was inhibited monophasically by cocaine, CFT, and Mazindol; the same potencies were observed with the three radioligands. Saturation analysis in the presence and in the absence of unlabeled inhibitor (CFT, Mazindol, cocaine) indicated a change in the Kd but not the Bmax, consonant with a competitive mechanism. Tris-HCl reduced the affinity of each radioligand and unlabeled inhibitor without changing the Bmax. N-Ethylmaleimide reduced the binding of all radioligands equally and cocaine offered protection. The dissociation rate of [3H]CFT and [3H]Mazindol binding was not affected by the presence of Mazindol and CFT, respectively. The Bmax of [3H]CFT and [3H]Mazindol binding was the same; the relatively higher value for [3H]GBR 12935 binding in analyses involving varying tritiated GBR 12935 only, was due primarily to an underestimation of the specific activity of [3H]GBR 12935. All results are in agreement with a one-site model in which cocaine, CFT, Mazindol, and GBR 12935 share a common binding site in mouse striatum.
Michael J Kuhar - One of the best experts on this subject based on the ideXlab platform.
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cocaine displaces 3h win 35 428 binding to dopamine uptake sites in vivo more rapidly than Mazindol or gbr 12909
European Journal of Pharmacology, 1991Co-Authors: Sakire Poḡun, Ursula Scheffel, Michael J KuharAbstract:Abstract Previous studies have shown that [ 3 H]WIN 35,428 binds preferentially to striatal cocaine receptors at the dopamine transporter after in vivo injection. In vivo binding competition studies were carried out to assess the relative rates of entry and occupancy of cocaine receptors by (−)-cocainc, Mazindol and GBR 12909. After i.v. injection, (−)-cocaine occupied receptors relatively more rapidly than GBR 12,909 while Mazindol was the slowest.
Katsuya Nagai - One of the best experts on this subject based on the ideXlab platform.
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effects of Mazindol on the hyperglycemia induced by intracranial injection of 2 deoxy d glucose or by oral glucose load in intact and diabetic rats
Journal of Clinical Biochemistry and Nutrition, 1998Co-Authors: Soojin Chun, Takaki Shima, Eiji Nagao, Katsuya NagaiAbstract:We previously found that Mazindol reduces food efficiency [=increase in body weight (g) per day/food intake (g) per day] in rats (Nagai et al., J Obesity Weight Regul., 4, 33-49, 1985). In order to elucidate the action of Mazindol with respect to food efficiency, the effects of its administration on the elevation of the blood glucose concentration induced by Intracranial injection of 2-deoxy-D-glucose (2DG) into intact rats, or by the imposition of an oral glucose load in intact and diabetic rats, were examined. We observed that peripheral, but not central, administration of Mazindol inhibited the hyperglycemia elicited by 2DG injection and enhanced glucose tolerance following an oral glucose load in diabetic rats, but not intact animals. These findings suggest that peripheral administration of Mazindol reduces the blood glucose concentration when it is elevated. Therefore, it is possible that the reductive effect of Mazindol on food efficiency might be induced by the enhancement of glucose uptake into cells of tissues such as skeletal muscle, since our previous work suggested that Mazindol increases glucose uptake into skeletal muscle cells (Nagai et al., Eur. J. Pharmacol., 260, 29-37, 1994),
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Mazindol enhances glucose uptake by rat skeletal muscle
European Journal of Pharmacology, 1994Co-Authors: Katsuya Nagai, Nobuo Nagai, Yasushi Isojima, Shunji Itoh, Nobuaki Okumura, Hachiro NakagawaAbstract:The pharmacological action of Mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5-imidazo[2,1-a]isoindol) was examined by studying its effect on glucose uptake by rat tissues using radiolabelled 2-deoxy-D-glucose. The following results were obtained. (1) The rate constant (Ki) of net tissue 2-deoxy-D-glucose uptake increased in the cerebral cortex (4.7-fold, P < 0.05), the hypothalamus (4.6-fold, P < 0.05), heart (4.0 fold, P < 0.05) and skeletal muscles (gastrocnemius, 5.7-fold, P < 0.01; soleus, 4.7-fold, P < 0.05), but not in epididymal adipose tissue in vivo 90 min after intragastric administration of Mazindol (20 mg/kg). (2) This increase in Ki values of net tissue 2-deoxy-D-glucose uptake was not observed after addition of Mazindol to the diet (40 mg/100 g of diet) for 4 days. (3) Mazindol (16.7 ng/ml to 16.7 μg/ml) stimulated 2-deoxy-D-glucose transport into sarcolemmal vesicles of the gastrocnemius muscle in vitro (1.6–1.8-fold, P < 0.05) and this stimulation was blocked by cytochalasin B (10 μM). These findings suggest that Mazindol stimulates glucose transport into skeletal muscles by acting on glucose transporters in the sarcolemmal membrane, and suggest that Mazindol may stimulate glucose transport into the brain and heart by a similar mechanism.
Sakire Poḡun - One of the best experts on this subject based on the ideXlab platform.
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cocaine displaces 3h win 35 428 binding to dopamine uptake sites in vivo more rapidly than Mazindol or gbr 12909
European Journal of Pharmacology, 1991Co-Authors: Sakire Poḡun, Ursula Scheffel, Michael J KuharAbstract:Abstract Previous studies have shown that [ 3 H]WIN 35,428 binds preferentially to striatal cocaine receptors at the dopamine transporter after in vivo injection. In vivo binding competition studies were carried out to assess the relative rates of entry and occupancy of cocaine receptors by (−)-cocainc, Mazindol and GBR 12909. After i.v. injection, (−)-cocaine occupied receptors relatively more rapidly than GBR 12,909 while Mazindol was the slowest.
Hachiro Nakagawa - One of the best experts on this subject based on the ideXlab platform.
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Mazindol enhances glucose uptake by rat skeletal muscle
European Journal of Pharmacology, 1994Co-Authors: Katsuya Nagai, Nobuo Nagai, Yasushi Isojima, Shunji Itoh, Nobuaki Okumura, Hachiro NakagawaAbstract:The pharmacological action of Mazindol (5-hydroxy-5-p-chlorophenyl-2,3-dihydro-5-imidazo[2,1-a]isoindol) was examined by studying its effect on glucose uptake by rat tissues using radiolabelled 2-deoxy-D-glucose. The following results were obtained. (1) The rate constant (Ki) of net tissue 2-deoxy-D-glucose uptake increased in the cerebral cortex (4.7-fold, P < 0.05), the hypothalamus (4.6-fold, P < 0.05), heart (4.0 fold, P < 0.05) and skeletal muscles (gastrocnemius, 5.7-fold, P < 0.01; soleus, 4.7-fold, P < 0.05), but not in epididymal adipose tissue in vivo 90 min after intragastric administration of Mazindol (20 mg/kg). (2) This increase in Ki values of net tissue 2-deoxy-D-glucose uptake was not observed after addition of Mazindol to the diet (40 mg/100 g of diet) for 4 days. (3) Mazindol (16.7 ng/ml to 16.7 μg/ml) stimulated 2-deoxy-D-glucose transport into sarcolemmal vesicles of the gastrocnemius muscle in vitro (1.6–1.8-fold, P < 0.05) and this stimulation was blocked by cytochalasin B (10 μM). These findings suggest that Mazindol stimulates glucose transport into skeletal muscles by acting on glucose transporters in the sarcolemmal membrane, and suggest that Mazindol may stimulate glucose transport into the brain and heart by a similar mechanism.
