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Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist.
Eur J Pharmacol. 2004 Oct 06; 501(1-3):111-9.EJ

Abstract

Biological studies were conducted on (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-isoquinoline-carboxamide (JDTic), the first potent kappa-selective opioid receptor antagonist not derived from an opiate class of compounds. In the mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked anticociceptive activity for up to 2 weeks. When JDTic was administered either s.c. or p.o. 24 h before the selective KOP (kappa)-opioid receptor agonist, enadoline, AD(50s) of 4.1 and 27.3, respectively, were obtained. A time-course study of JDTic versus enadoline indicated significant antagonist p.o. activity up to 28 days. In contrast, JDTic, s.c., failed to antagonize the analgesic effects of the selective MOP mu-opioid receptor agonist, sufentanil. In the squirrel monkey shock titration antinociception test, JDTic given intramuscularly (i.m.) shifted the trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide (U50,488) dose-effect curve to the right. In the U50,488-induced diuresis rat test, JDTic, s.c., suppressed diuretic activity with a greater potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long- and orally acting selective kappa-opioid antagonist.

Authors+Show Affiliations

Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina, USA. fic@rti.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15464069

Citation

Carroll, Ivy, et al. "Pharmacological Properties of JDTic: a Novel Kappa-opioid Receptor Antagonist." European Journal of Pharmacology, vol. 501, no. 1-3, 2004, pp. 111-9.
Carroll I, Thomas JB, Dykstra LA, et al. Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist. Eur J Pharmacol. 2004;501(1-3):111-9.
Carroll, I., Thomas, J. B., Dykstra, L. A., Granger, A. L., Allen, R. M., Howard, J. L., Pollard, G. T., Aceto, M. D., & Harris, L. S. (2004). Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist. European Journal of Pharmacology, 501(1-3), 111-9.
Carroll I, et al. Pharmacological Properties of JDTic: a Novel Kappa-opioid Receptor Antagonist. Eur J Pharmacol. 2004 Oct 6;501(1-3):111-9. PubMed PMID: 15464069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist. AU - Carroll,Ivy, AU - Thomas,James B, AU - Dykstra,Linda A, AU - Granger,Arthur L, AU - Allen,Richard M, AU - Howard,James L, AU - Pollard,Gerald T, AU - Aceto,Mario D, AU - Harris,Louis S, PY - 2004/06/03/received PY - 2004/08/03/revised PY - 2004/08/05/accepted PY - 2004/10/7/pubmed PY - 2005/3/5/medline PY - 2004/10/7/entrez SP - 111 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 501 IS - 1-3 N2 - Biological studies were conducted on (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-isoquinoline-carboxamide (JDTic), the first potent kappa-selective opioid receptor antagonist not derived from an opiate class of compounds. In the mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked anticociceptive activity for up to 2 weeks. When JDTic was administered either s.c. or p.o. 24 h before the selective KOP (kappa)-opioid receptor agonist, enadoline, AD(50s) of 4.1 and 27.3, respectively, were obtained. A time-course study of JDTic versus enadoline indicated significant antagonist p.o. activity up to 28 days. In contrast, JDTic, s.c., failed to antagonize the analgesic effects of the selective MOP mu-opioid receptor agonist, sufentanil. In the squirrel monkey shock titration antinociception test, JDTic given intramuscularly (i.m.) shifted the trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide (U50,488) dose-effect curve to the right. In the U50,488-induced diuresis rat test, JDTic, s.c., suppressed diuretic activity with a greater potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long- and orally acting selective kappa-opioid antagonist. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15464069/Pharmacological_properties_of_JDTic:_a_novel_kappa_opioid_receptor_antagonist_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(04)00926-4 DB - PRIME DP - Unbound Medicine ER -