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Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in vivo studies.
J Pharmacol Exp Ther. 2007 Jun; 321(3):968-74.JP

Abstract

The excellent pharmacological profile displayed by the selective nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol] in vitro prompted us to investigate the actions of this compound in vivo. In the mouse tail withdrawal assay, SB-612111 given i.p. up to 3 mg/kg did not modify per se tail withdrawal latencies but was able to prevent the pronociceptive and the antinociceptive action of 1 nmol of N/OFQ given i.c.v. and i.t., respectively. In food intake studies performed in sated mice, SB-612111 (1 mg/kg i.p.) had no effect on food consumption but fully prevented the orexigenic effect of 1 nmol of N/OFQ i.c.v. In 17-h food-deprived mice, the opioid receptor antagonist naltrexone (1 mg/kg s.c.), but not SB-612111 (1 and 10 mg/kg i.p.), produced a statistically significant reduction of food intake. In the mouse forced swimming and tail suspension tests, SB-612111 (1-10 mg/kg) reduced immobility time. The antidepressant-like effect elicited by SB-612111 in the forced swimming test was reversed by the i.c.v. injection of 1 nmol of N/OFQ and no longer evident in mice knockout for the NOP receptor gene. In conclusion, the present findings demonstrate that SB-612111 behaves in vivo as a potent and selective NOP antagonist and suggest that the N/OFQ-NOP receptor endogenous system plays an important role in regulating mood-related behaviors. The use of SB-612111 in future pathophysiological studies will certainly contribute to define the therapeutic potential of selective NOP receptor antagonists in different disease areas.

Authors+Show Affiliations

Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, Ferrara, Italy.No 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)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17329551

Citation

Rizzi, Anna, et al. "Pharmacological Characterization of the Nociceptin/orphanin FQ Receptor Antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in Vivo Studies." The Journal of Pharmacology and Experimental Therapeutics, vol. 321, no. 3, 2007, pp. 968-74.
Rizzi A, Gavioli EC, Marzola G, et al. Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in vivo studies. J Pharmacol Exp Ther. 2007;321(3):968-74.
Rizzi, A., Gavioli, E. C., Marzola, G., Spagnolo, B., Zucchini, S., Ciccocioppo, R., Trapella, C., Regoli, D., & Calò, G. (2007). Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in vivo studies. The Journal of Pharmacology and Experimental Therapeutics, 321(3), 968-74.
Rizzi A, et al. Pharmacological Characterization of the Nociceptin/orphanin FQ Receptor Antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in Vivo Studies. J Pharmacol Exp Ther. 2007;321(3):968-74. PubMed PMID: 17329551.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological characterization of the nociceptin/orphanin FQ receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol]: in vivo studies. AU - Rizzi,Anna, AU - Gavioli,Elaine C, AU - Marzola,Giuliano, AU - Spagnolo,Barbara, AU - Zucchini,Silvia, AU - Ciccocioppo,Roberto, AU - Trapella,Claudio, AU - Regoli,Domenico, AU - Calò,Girolamo, Y1 - 2007/02/28/ PY - 2007/3/3/pubmed PY - 2007/7/31/medline PY - 2007/3/3/entrez SP - 968 EP - 74 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 321 IS - 3 N2 - The excellent pharmacological profile displayed by the selective nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonist SB-612111 [(-)-cis-1-methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol] in vitro prompted us to investigate the actions of this compound in vivo. In the mouse tail withdrawal assay, SB-612111 given i.p. up to 3 mg/kg did not modify per se tail withdrawal latencies but was able to prevent the pronociceptive and the antinociceptive action of 1 nmol of N/OFQ given i.c.v. and i.t., respectively. In food intake studies performed in sated mice, SB-612111 (1 mg/kg i.p.) had no effect on food consumption but fully prevented the orexigenic effect of 1 nmol of N/OFQ i.c.v. In 17-h food-deprived mice, the opioid receptor antagonist naltrexone (1 mg/kg s.c.), but not SB-612111 (1 and 10 mg/kg i.p.), produced a statistically significant reduction of food intake. In the mouse forced swimming and tail suspension tests, SB-612111 (1-10 mg/kg) reduced immobility time. The antidepressant-like effect elicited by SB-612111 in the forced swimming test was reversed by the i.c.v. injection of 1 nmol of N/OFQ and no longer evident in mice knockout for the NOP receptor gene. In conclusion, the present findings demonstrate that SB-612111 behaves in vivo as a potent and selective NOP antagonist and suggest that the N/OFQ-NOP receptor endogenous system plays an important role in regulating mood-related behaviors. The use of SB-612111 in future pathophysiological studies will certainly contribute to define the therapeutic potential of selective NOP receptor antagonists in different disease areas. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/17329551/Pharmacological_characterization_of_the_nociceptin/orphanin_FQ_receptor_antagonist_SB_612111_[____cis_1_methyl_7_[[4__26_dichlorophenyl_piperidin_1_yl]methyl]_6789_tetrahydro_5H_benzocyclohepten_5_ol]:_in_vivo_studies_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17329551 DB - PRIME DP - Unbound Medicine ER -