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Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors.
Eur J Pharmacol. 2004 Jul 08; 495(1):43-53.EJ

Abstract

The pharmacology of 3-(2-ethylmorpholino)-5,5'-di(p-bromophenyl)-imidazolidinedione (DML20), 3-(1-hydroxypropyl)-5,5'-di(p-bromophenyl)-imidazolidinedione (DML21) and 3-heptyl-5,5'-di(p-bromophenyl)-imidazolidinedione (DML23) was extended by studying affinity and GTP binding modulation on cannabinoid receptor subtypes (CB1 and CB2) from rat tissues and human cannabinoid receptors expressed in Chinese Hamster Ovary cells. Competitive binding studies indicated that DML20, DML21 and DML23 are selective ligands for cannabinoid CB1 receptors. In rat cerebellum homogenates, DML20, DML21 and DML23 were unable to influence [35S]GTPgammaS binding but competitively inhibit HU 210-induced [35S]GTPgammaS binding (pKB of 6.11 +/- 0.14, 6.25 +/- 0.06 and 5.74 +/- 0.09, respectively), indicating that they act as cannabinoid CB1 receptor neutral antagonists. However, in CHO cells homogenates expressing selectively either human cannabinoid CB1 or CB2 receptors, they behaved as inverse agonists decreasing the [35S]GTPgammaS binding, with similar efficacy. In conclusion, these derivatives exhibit different activities (neutral antagonism and inverse agonism) in the different models of cannabinoid receptors studied.

Authors+Show Affiliations

Unité de Chimie pharmaceutique et de Radiopharmacie (73.40) Ecole de Pharmacie, Université Catholique de Louvain, 73, Avenue E. Mounier, UCL-CMFA 7340, B-1200 Bruxelles, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15219819

Citation

Govaerts, Sophie J., et al. "Characterization of the Pharmacology of Imidazolidinedione Derivatives at Cannabinoid CB1 and CB2 Receptors." European Journal of Pharmacology, vol. 495, no. 1, 2004, pp. 43-53.
Govaerts SJ, Muccioli GG, Hermans E, et al. Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors. Eur J Pharmacol. 2004;495(1):43-53.
Govaerts, S. J., Muccioli, G. G., Hermans, E., & Lambert, D. M. (2004). Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors. European Journal of Pharmacology, 495(1), 43-53.
Govaerts SJ, et al. Characterization of the Pharmacology of Imidazolidinedione Derivatives at Cannabinoid CB1 and CB2 Receptors. Eur J Pharmacol. 2004 Jul 8;495(1):43-53. PubMed PMID: 15219819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of the pharmacology of imidazolidinedione derivatives at cannabinoid CB1 and CB2 receptors. AU - Govaerts,Sophie J, AU - Muccioli,Giulio G, AU - Hermans,Emmanuel, AU - Lambert,Didier M, PY - 2004/05/06/received PY - 2004/05/12/accepted PY - 2004/6/29/pubmed PY - 2005/7/27/medline PY - 2004/6/29/entrez SP - 43 EP - 53 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 495 IS - 1 N2 - The pharmacology of 3-(2-ethylmorpholino)-5,5'-di(p-bromophenyl)-imidazolidinedione (DML20), 3-(1-hydroxypropyl)-5,5'-di(p-bromophenyl)-imidazolidinedione (DML21) and 3-heptyl-5,5'-di(p-bromophenyl)-imidazolidinedione (DML23) was extended by studying affinity and GTP binding modulation on cannabinoid receptor subtypes (CB1 and CB2) from rat tissues and human cannabinoid receptors expressed in Chinese Hamster Ovary cells. Competitive binding studies indicated that DML20, DML21 and DML23 are selective ligands for cannabinoid CB1 receptors. In rat cerebellum homogenates, DML20, DML21 and DML23 were unable to influence [35S]GTPgammaS binding but competitively inhibit HU 210-induced [35S]GTPgammaS binding (pKB of 6.11 +/- 0.14, 6.25 +/- 0.06 and 5.74 +/- 0.09, respectively), indicating that they act as cannabinoid CB1 receptor neutral antagonists. However, in CHO cells homogenates expressing selectively either human cannabinoid CB1 or CB2 receptors, they behaved as inverse agonists decreasing the [35S]GTPgammaS binding, with similar efficacy. In conclusion, these derivatives exhibit different activities (neutral antagonism and inverse agonism) in the different models of cannabinoid receptors studied. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15219819/Characterization_of_the_pharmacology_of_imidazolidinedione_derivatives_at_cannabinoid_CB1_and_CB2_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299904005175 DB - PRIME DP - Unbound Medicine ER -