The Experts below are selected from a list of 15966 Experts worldwide ranked by ideXlab platform
Huidi Jiang - One of the best experts on this subject based on the ideXlab platform.
-
Multiple organic cation transporters contribute to the renal transport of Sulpiride
Biopharmaceutics & drug disposition, 2017Co-Authors: Yayun Weng, Mengru Bai, Wei Wang, Hongmei Lei, Hui Zhou, Huidi JiangAbstract:Sulpiride, a selective dopamine D2 receptor blocker, is used widely for the treatment of schizophrenia, depression and gastric/duodenal ulcers. Because the great majority of Sulpiride is positively charged at physiological pH 7.4, and ~70% of the dose recovered in urine is in the unchanged form after human intravenous administration of Sulpiride, it is believed that transporters play an important role in the renal excretion of Sulpiride. The aim of the present study was to explore which transporters contribute to the renal disposition of Sulpiride. The results demonstrated that Sulpiride was a substrate of human carnitine/organic cation transporter 1 (hOCTN1) and 2 (hOCTN2), human organic cation transporter 2 (hOCT2), human multidrug and toxin efflux extrusion protein 1 (hMATE1) and 2-K (hMATE2-K). Sulpiride accumulation from the basolateral (BL) to the apical (AP) side in MDCK-hOCT2/pcDNA3.1 cell monolayers was much greater than that in MDCK-hOCT2/hMATE1 cells, and cimetidine dramatically reduced the intracellular accumulation of Sulpiride from BL to AP. In addition, the accumulation of Sulpiride in mouse primary renal tubular cells (mPRTCs) was markedly reduced by inhibitors of Oct2 and Octns. The results implied that OCTN1, OCTN2, OCT2, MATE1 and MATE2-K probably contributed to the renal transfer of Sulpiride, in which OCT2 mediated the uptake of Sulpiride from the bloodstream to the proximal tubular cells, while MATEs contributed to the Sulpiride efflux from the proximal tubular cells to the renal lumen, and OCTNs participated in both renal secretion and reabsorption.
-
Multiple drug transporters mediate the placental transport of Sulpiride.
Archives of toxicology, 2017Co-Authors: Mengru Bai, Dongli Sun, Caihong Zheng, Yayun Weng, Xi Yang, Ting Jiang, Huidi JiangAbstract:Sulpiride is a typical antipsychotic drug for the treatment of schizophrenia, depression and other psychological disorders. It has been proven that a small amount of Sulpiride could cross the human placenta using an ex vivo placental perfusion model. However, the placental transfer mechanism has not been elucidated. Considering the structure of Sulpiride, we speculated that the transporters expressed in placenta might be involved in Sulpiride uptake across the blood–placenta barrier. The aim of our study was to determine which transporters contributed to the placental transfer of Sulpiride. Our results revealed that Sulpiride was a substrate of human organic cation transporter (hOCT) 3, human multidrug resistance protein (hMDR) 1 and human breast cancer resistance protein (hBCRP) using transfected cells expressing respective transporters. In addition, the accumulation of Sulpiride in BeWo cells (a human choriocarcinoma cell line) was obviously affected by inhibitors of carnitine/organic cation transporter (OCTN) 2, MDR1 and BCRP. The accumulation of Sulpiride in primary human trophoblast cells was obviously affected by inhibitors of OCT3, OCTN1 and OCTN2. The above results indicate that hOCTN1 and hOCTN2 likely contribute to the Sulpiride uptake from maternal circulation to trophoblast cells, while hMDR1 and hBCRP mediate the efflux from trophoblast cells to maternal circulation, and hOCT3 probably is involved in the bidirectional transport of Sulpiride between the placenta and fetal blood.
Yayun Weng - One of the best experts on this subject based on the ideXlab platform.
-
Multiple organic cation transporters contribute to the renal transport of Sulpiride
Biopharmaceutics & drug disposition, 2017Co-Authors: Yayun Weng, Mengru Bai, Wei Wang, Hongmei Lei, Hui Zhou, Huidi JiangAbstract:Sulpiride, a selective dopamine D2 receptor blocker, is used widely for the treatment of schizophrenia, depression and gastric/duodenal ulcers. Because the great majority of Sulpiride is positively charged at physiological pH 7.4, and ~70% of the dose recovered in urine is in the unchanged form after human intravenous administration of Sulpiride, it is believed that transporters play an important role in the renal excretion of Sulpiride. The aim of the present study was to explore which transporters contribute to the renal disposition of Sulpiride. The results demonstrated that Sulpiride was a substrate of human carnitine/organic cation transporter 1 (hOCTN1) and 2 (hOCTN2), human organic cation transporter 2 (hOCT2), human multidrug and toxin efflux extrusion protein 1 (hMATE1) and 2-K (hMATE2-K). Sulpiride accumulation from the basolateral (BL) to the apical (AP) side in MDCK-hOCT2/pcDNA3.1 cell monolayers was much greater than that in MDCK-hOCT2/hMATE1 cells, and cimetidine dramatically reduced the intracellular accumulation of Sulpiride from BL to AP. In addition, the accumulation of Sulpiride in mouse primary renal tubular cells (mPRTCs) was markedly reduced by inhibitors of Oct2 and Octns. The results implied that OCTN1, OCTN2, OCT2, MATE1 and MATE2-K probably contributed to the renal transfer of Sulpiride, in which OCT2 mediated the uptake of Sulpiride from the bloodstream to the proximal tubular cells, while MATEs contributed to the Sulpiride efflux from the proximal tubular cells to the renal lumen, and OCTNs participated in both renal secretion and reabsorption.
-
Multiple drug transporters mediate the placental transport of Sulpiride.
Archives of toxicology, 2017Co-Authors: Mengru Bai, Dongli Sun, Caihong Zheng, Yayun Weng, Xi Yang, Ting Jiang, Huidi JiangAbstract:Sulpiride is a typical antipsychotic drug for the treatment of schizophrenia, depression and other psychological disorders. It has been proven that a small amount of Sulpiride could cross the human placenta using an ex vivo placental perfusion model. However, the placental transfer mechanism has not been elucidated. Considering the structure of Sulpiride, we speculated that the transporters expressed in placenta might be involved in Sulpiride uptake across the blood–placenta barrier. The aim of our study was to determine which transporters contributed to the placental transfer of Sulpiride. Our results revealed that Sulpiride was a substrate of human organic cation transporter (hOCT) 3, human multidrug resistance protein (hMDR) 1 and human breast cancer resistance protein (hBCRP) using transfected cells expressing respective transporters. In addition, the accumulation of Sulpiride in BeWo cells (a human choriocarcinoma cell line) was obviously affected by inhibitors of carnitine/organic cation transporter (OCTN) 2, MDR1 and BCRP. The accumulation of Sulpiride in primary human trophoblast cells was obviously affected by inhibitors of OCT3, OCTN1 and OCTN2. The above results indicate that hOCTN1 and hOCTN2 likely contribute to the Sulpiride uptake from maternal circulation to trophoblast cells, while hMDR1 and hBCRP mediate the efflux from trophoblast cells to maternal circulation, and hOCT3 probably is involved in the bidirectional transport of Sulpiride between the placenta and fetal blood.
Luis Hernandez - One of the best experts on this subject based on the ideXlab platform.
-
the antipsychotic drug Sulpiride does not affect bodyweight in male rats is insulin resistance involved
European Journal of Pharmacology, 2002Co-Authors: Trino Baptista, Luis Hernandez, Ximena Páez, Anny Lacruz, Serge BeaulieuAbstract:Previous studies have shown that prolonged administration of antipsychotic drugs induces obesity in female but not in male rats. To explore the mechanisms involved in this sex-dependent effect, we administered the dopamine antagonist Sulpiride (20 mg/kg i.p.) or vehicle (0.1 N HCl) to adult male rats during 21 days and daily assessed bodyweight and food intake. Then, we evaluated the glucose tolerance and the serum levels of insulin, leptin, total testosterone, dehydroepiandrosterone-sulfate (DHEA-S), thyroid hormones and blood lipids. In another experiment, food intake and water intake were assessed after acute injections of Sulpiride or vehicle into the perifornical lateral hypothalamus. Lastly, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) in the lateral hypothalamus were assessed by in vivo microdialysis after acute systemic injections of Sulpiride and vehicle. Chronic Sulpiride administration did not affect bodyweight gain and food intake. However, prolactin levels and the area under the glucose and insulin curves were significantly elevated. Acute Sulpiride significantly increased food intake, water intake, DOPAC and HVA levels. The acute effects of Sulpiride show that this drug is active at the perifornical lateral hypothalamus, which is a brain area where blockade of dopamine receptors stimulates feeding. However, after prolonged administration, Sulpiride did not affect body weight. This lack of effect may be related to the impairment of insulin sensitivity, which may prevent body weight gain, and counteract other effects of Sulpiride that promote adiposity such as hyperprolactinemia. These findings noticeably contrast with those observed in Sulpiride-treated female rats that appear to display enhanced insulin sensitivity. The changes in insulin sensitivity do not appear related to a decrease in androgenic activity, because testosterone and DHEA-S levels were not affected by Sulpiride. However, these results should be considered as preliminary because other relevant endocrine variables such as free testosterone, steroid binding globulin and pituitary gonadotrophin levels were not evaluated. Since the same sex-dependent effect on body weight and food intake in rats has been observed during administration of risperidone, which has a different pharmacological profile than Sulpiride, future studies must evaluate other neurotransmitters involved in food intake regulation such as serotonin, noradrenaline and histamine.
-
Enhancement of amphetamine anorexia after chronic administration of Sulpiride in rats
Pharmacology biochemistry and behavior, 1993Co-Authors: Trino Baptista, Luis Teneud, Luis HernandezAbstract:Abstract Long-term administration of Sulpiride induces hyperphagia and obesity in female rats. After Sulpiride withdrawal, a significant hypophagia has been observed. The hyperphagia could be related to the blockade and the hypophagia to supersensitivity of dopamine D 2 receptors, in particular those D 2 receptors located in the perifornical hypothalamus. If this were the case, an enhancement of anorexia induced by amphetamine and dopamine should be observed after interruption of long-term supiride treatment. Two doses of systemic Sulpiride (20 or 200 mg/kg) and one dose of intrahypothalamic Sulpiride (15 μg) were tested. Amphetamine was administered by systemic or intrahypothalamic infusion. Dopamine was administered in the hypothalamus. After withdrawal of systemic administration of Sulpiride (200 mg/kg), an enhancement of anorexia induced by systemic amphetamine was observed. However, the anorexia induced by intrahypothalamic injections of amphetamine or dopamine was not affected by the interruption of the Sulpiride treatment. These results suggest that the hypophagia following chronic Sulpiride treatment is not due to supersensitivity of D 2 dopamine receptors in the lateral hypothalamus. Moreover, the change in the response to amphetamine might be related to supersensitivity of extrahypothalamic D 2 receptors.
Mengru Bai - One of the best experts on this subject based on the ideXlab platform.
-
Multiple organic cation transporters contribute to the renal transport of Sulpiride
Biopharmaceutics & drug disposition, 2017Co-Authors: Yayun Weng, Mengru Bai, Wei Wang, Hongmei Lei, Hui Zhou, Huidi JiangAbstract:Sulpiride, a selective dopamine D2 receptor blocker, is used widely for the treatment of schizophrenia, depression and gastric/duodenal ulcers. Because the great majority of Sulpiride is positively charged at physiological pH 7.4, and ~70% of the dose recovered in urine is in the unchanged form after human intravenous administration of Sulpiride, it is believed that transporters play an important role in the renal excretion of Sulpiride. The aim of the present study was to explore which transporters contribute to the renal disposition of Sulpiride. The results demonstrated that Sulpiride was a substrate of human carnitine/organic cation transporter 1 (hOCTN1) and 2 (hOCTN2), human organic cation transporter 2 (hOCT2), human multidrug and toxin efflux extrusion protein 1 (hMATE1) and 2-K (hMATE2-K). Sulpiride accumulation from the basolateral (BL) to the apical (AP) side in MDCK-hOCT2/pcDNA3.1 cell monolayers was much greater than that in MDCK-hOCT2/hMATE1 cells, and cimetidine dramatically reduced the intracellular accumulation of Sulpiride from BL to AP. In addition, the accumulation of Sulpiride in mouse primary renal tubular cells (mPRTCs) was markedly reduced by inhibitors of Oct2 and Octns. The results implied that OCTN1, OCTN2, OCT2, MATE1 and MATE2-K probably contributed to the renal transfer of Sulpiride, in which OCT2 mediated the uptake of Sulpiride from the bloodstream to the proximal tubular cells, while MATEs contributed to the Sulpiride efflux from the proximal tubular cells to the renal lumen, and OCTNs participated in both renal secretion and reabsorption.
-
Multiple drug transporters mediate the placental transport of Sulpiride.
Archives of toxicology, 2017Co-Authors: Mengru Bai, Dongli Sun, Caihong Zheng, Yayun Weng, Xi Yang, Ting Jiang, Huidi JiangAbstract:Sulpiride is a typical antipsychotic drug for the treatment of schizophrenia, depression and other psychological disorders. It has been proven that a small amount of Sulpiride could cross the human placenta using an ex vivo placental perfusion model. However, the placental transfer mechanism has not been elucidated. Considering the structure of Sulpiride, we speculated that the transporters expressed in placenta might be involved in Sulpiride uptake across the blood–placenta barrier. The aim of our study was to determine which transporters contributed to the placental transfer of Sulpiride. Our results revealed that Sulpiride was a substrate of human organic cation transporter (hOCT) 3, human multidrug resistance protein (hMDR) 1 and human breast cancer resistance protein (hBCRP) using transfected cells expressing respective transporters. In addition, the accumulation of Sulpiride in BeWo cells (a human choriocarcinoma cell line) was obviously affected by inhibitors of carnitine/organic cation transporter (OCTN) 2, MDR1 and BCRP. The accumulation of Sulpiride in primary human trophoblast cells was obviously affected by inhibitors of OCT3, OCTN1 and OCTN2. The above results indicate that hOCTN1 and hOCTN2 likely contribute to the Sulpiride uptake from maternal circulation to trophoblast cells, while hMDR1 and hBCRP mediate the efflux from trophoblast cells to maternal circulation, and hOCT3 probably is involved in the bidirectional transport of Sulpiride between the placenta and fetal blood.
E Mussini - One of the best experts on this subject based on the ideXlab platform.
-
the effects of s and r Sulpiride metoclopramide cisapride and domperidone on the small intestine suggest da2 receptors are involved in the control of small intestinal transit time in rats
Pharmacological Research, 1992Co-Authors: Ettore Zuccato, Cristina Bertolo, Monica Salomoni, Angelo Forgione, E MussiniAbstract:Summary To study the effect of intraperitoneal S(−)Sulpiride (1–15 mg/kg), R(+)Sulpiride (5–10 mg/kg), metoclopramide (1–15 mg/kg), cisapride (10 mg/kg) and domperidone (5–10 mg/kg) on intestinal progression, rats were given the test drug followed by oral lactulose. Their hydrogen excretion was used to calculate the small bowel transit time (SBTT) and maximum peak time (MPT). Metoclopramide (7.5 mg/kg) had the greatest effect on SBTT (−25%), followed by S(−)Sulpiride and domperidone. S(−)Sulpiride (10 mg/kg) had the greatest activity on the MPT (−35.2%) followed by metoclopramide. R(+)Sulpiride and cisapride did not modify SBTT and MPT. In conclusion S(−)Sulpiride is the isomer active on intestinal transit and DA 2 -receptors seem important targets in the modulation of intestinal progression, since S(−)Sulpiride, metoclopramide and domperidone are DA 2 -receptor antagonists, and R(+)Sulpiride and cisapride are not. The H 2 breath test proved a valid method for measuring the effect of drugs on the small intestine in animals.
