JDTic

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JDTic
JDTic.png
IUPAC ime
(3R)-7-hydroxy- N-((1S)-1[(3R,4R)-4- (3-hydroxyphenyl)- 3,4-dimethylpiperidin- 1-yl]methyl 2-methylpropyl)- 1,2,3,4-tetrahydroisoquinoline- 3-carboxamide
Identifikatori
CAS broj361444-66-8 ДаY
785835-79-2 (hidrohlorid)
PubChemCID 9956146
SinonimiJDTic
Hemijski podaci
FormulaC28H39N3O3
Molarna masa465.626 g/mol

JDTic je lek, koji je visoko selektivni κ-opioidni antagonist. On blokira taj receptor bez vršenja uticaja na μ- ili δ- opioidne receptore.[1] On je derivat 4-fenilpiperidina, koji je u nekoj meri strukturno srodan sa analgeticima kao što su meperidin i ketobemidon, i bliže sa mi opioidnim antagonistom alvimopanom. On se strukturno razlikuje od drugih kapa antagonist,a kao što je norbinaltorfimin.[2][3]

On ima veoma dugo vreme dejstva, sa efektima na životinjama primetnim do nekoliko nedelja nakon administracije jedne doze,[4] mada njegovo vezivanje za kapa opioidni receptor nije nepovratno i njegovi dugotrajno dejstvo je umesto toga uzrokovano promenama aktivnosti c-Jun N-terminalne kinaze.[5] Iz životinjska ispitivanja proizilazi da on može da proizvede antidepresantske i anksioloitičke efekte,[6] kao i da može da ima primenu u lečenju adikcije na kokain i morfin.[7][8]

Vidi još[уреди]

Reference[уреди]

  1. ^ Thomas JB, Atkinson RN, Rothman RB, Fix SE, Mascarella SW, Vinson NA, Xu H, Dersch CM, Lu Y, Cantrell BE, Zimmerman DM, Carroll FI. Identification of the first trans-(3R,4R)- dimethyl-4-(3-hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity. Journal of Medicinal Chemistry. 2001 Aug 16;44(17):2687-90. PMID 11495579
  2. ^ Thomas JB, Atkinson RN, Vinson NA, Catanzaro JL, Perretta CL, Fix SE, Mascarella SW, Rothman RB, Xu H, Dersch CM, Cantrell BE, Zimmerman DM, Carroll FI. Identification of (3R)-7-hydroxy- N-((1S)-1-(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl- 1-piperidinylmethyl- 2-methylpropyl)- 1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide as a novel potent and selective opioid kappa receptor antagonist. Journal of Medicinal Chemistry. 2003 Jul 3;46(14):3127-37. PMID 12825951
  3. ^ Cai TB, Zou Z, Thomas JB, Brieaddy L, Navarro HA, Carroll FI. Synthesis and in vitro opioid receptor functional antagonism of analogues of the selective kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1[(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl- 1-piperidinyl]methyl 2-methylpropyl)- 1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide (JDTic). Journal of Medicinal Chemistry. 2008 Mar 27;51(6):1849-60. PMID 18307295
  4. ^ Carroll FI, Thomas JB, Dykstra LA, Granger AL, Allen RM, Howard JL, Pollard GT, Aceto MD, Harris LS. Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist. European Journal of Pharmacology. 2004 Oct 6;501(1-3):111-9. PMID 15464069
  5. ^ Bruchas MR, Yang T, Schreiber S, Defino M, Kwan SC, Li S, Chavkin C. Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase. Journal of Biological Chemistry. 2007 Oct 12;282(41):29803-11. DOI 10.1074/jbc.M705540200 PMID 17702750
  6. ^ Knoll AT, Meloni EG, Thomas JB, Carroll FI, Carlezon WA Jr. Anxiolytic-like effects of kappa-opioid receptor antagonists in models of unlearned and learned fear in rats. Journal of Pharmacology and Experimental Therapeutics. 2007 Dec;323(3):838-45. PMID 17823306
  7. ^ Beardsley PM, Howard JL, Shelton KL, Carroll FI. Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats. Psychopharmacology (Berlin). 2005 Nov;183(1):118-26. DOI 10.1007/s00213-005-0167-4 PMID 16184376
  8. ^ Carroll FI, Harris LS, Aceto MD. Effects of JDTic, a selective kappa-opioid receptor antagonist, on the development and expression of physical dependence on morphine using a rat continuous-infusion model. European Journal of Pharmacology. 2005 Nov 7;524(1-3):89-94. PMID 16236279

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