On August 25, 2016, Damont, Annelaure; Goutal, Sebastien; Auvity, Sylvain; Valette, Heric; Kuhnast, Bertrand; Saba, Wadad; Tournier, Nicolas published an article.Reference of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Imaging the impact of cyclosporin A and dipyridamole on P-glycoprotein (ABCB1) function at the blood-brain barrier: A [11C]-N-desmethyl-loperamide PET study in nonhuman primates. And the article contained the following:
Cyclosporin A (CsA) and dipyridamole (DPy) are potent inhibitors of the P-glycoprotein (P-gp; ABCB1) in vitro. Their efficacy at inhibiting P-gp at the blood-brain barrier (BBB) is difficult to predict. Efficient and readily available (i.e. marketed) P-gp inhibitors are needed as probes to investigate the role of P-gp at the human BBB. In this study, the P-gp inhibition potency at the BBB of therapeutic doses of CsA or DPy was evaluated in baboons using Positron Emission Tomog. (PET) imaging with [11C]-N-desmethyl-loperamide ([11C]dLop), a radiolabeled P-gp substrate. The preparation of dLop as authentic standard and [11C]dLop as radiotracer were revisited so as to improve their production yields. [11C]dLop PET imaging was performed in the absence (n = 3, baseline condition) and the presence of CsA (15 mg/kg/h i.v., n = 3). Three animals were injected with i.v. DPy at either 0.56 or 0.96 or 2 mg/kg (n = 1), corresponding to the usual, maximal and twice the maximal dose in patients, resp., administered immediately before PET. [11C]dLop brain kinetics as well as [11C]dLop kinetics and radiometabolites in arterial plasma were measured to calculate [11C]dLop area-under the time-activity curve from 10 to 30 min in the brain (AUCbrain) and in plasma (AUCplasma). [11C]dLop brain uptake was described by AUCR = AUCbrain/AUCplasma. CsA as well as DPy did not measurably influence [11C]dLop plasma kinetics and metabolism Baseline AUCR (0.85 ± 0.29) was significantly enhanced in the presence of CsA (AUCR = 10.8 ± 3.6). Injection of pharmacol. dose of DPy did not enhance [11C]dLop brain distribution with AUCR being 1.2, 0.9 and 1.1 after administration of 0.56, 0.96 and 2 mg/kg DPy doses, resp. We used [11C]dLop PET imaging in baboons, a relevant in vivo model of P-gp function at the BBB, to show the P-gp inhibition potency of therapeutic dose CsA. Despite in vitro P-gp inhibition potency, usual doses DPy are not likely to inhibit P-gp function at the BBB. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Reference of 4-(4-Chlorophenyl)piperidin-4-ol
The Article related to cyclosporin a dipyridamole pgp inhibitor abcb1 drug interaction, bbb, drug-drug interaction, positron emission tomography, radiochemistry, stress-test, Pharmacology: Effects Of Inflammation Inhibitors and Immune Agents and other aspects.Reference of 4-(4-Chlorophenyl)piperidin-4-ol
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem