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Characterization of nociceptin/orphanin FQ-induced pain responses by the novel receptor antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride.
J Pharmacol Exp Ther. 2002 Oct; 303(1):424-30.JP

Abstract

At the spinal level, nociceptin/orphanin FQ (Noc/OFQ) produces pronociceptive and allodynic effects at low doses (picogram range), while causing antinociceptive effects at high doses (microgram range). The discrepancy of pain modulation by Noc/OFQ at low and high doses raised a question whether Noc/OFQ exerted actions through the same Noc/OFQ receptor. In the present study, we examined the involvement of the Noc/OFQ receptor in pain responses with the novel nonpeptide antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride (JTC-801). Allodynia and hyperalgesia evoked by intrathecal administration of Noc/OFQ (50 pg/mouse) were dose dependently blocked by simultaneous administration of JTC-801 with IC(50) values of 32.2 and 363 pg, respectively. JTC-801 did not induce allodynia by itself. Subcutaneous injection of formalin into a hindpaw evoked biphasic pain behaviors such as flinching and biting in mice. Noc/OFQ at 10 pg increased the second-phase pain behaviors evoked by 1% formalin, whereas it strongly inhibited both the first-phase and second-phase pain evoked by 2% formalin at 1 microg. Although the pronociceptive effect by 10 pg of Noc/OFQ was dose dependently blocked by JTC-801 with an IC(50) value of 4.58 pg, the antinociceptive effects by 1 microg of Noc/OFQ were not antagonized by JTC-801. Furthermore, both phases of 2% formalin-induced pain behaviors were relieved by JTC-801. These results demonstrate that pronociceptive responses induced by a low dose of Noc/OFQ may be mediated through the Noc/OFQ receptor in the spinal cord and that JTC-801 can be a useful antagonist to examine the involvement of endogenous Noc/OFQ and mediation of the Noc/OFQ receptor under physiological and pathophysiological conditions including pain.

Authors+Show Affiliations

Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.No 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, Non-U.S. Gov't

Language

eng

PubMed ID

12235279

Citation

Muratani, Tadatoshi, et al. "Characterization of Nociceptin/orphanin FQ-induced Pain Responses By the Novel Receptor Antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) Benzamide Monohydrochloride." The Journal of Pharmacology and Experimental Therapeutics, vol. 303, no. 1, 2002, pp. 424-30.
Muratani T, Minami T, Enomoto U, et al. Characterization of nociceptin/orphanin FQ-induced pain responses by the novel receptor antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride. J Pharmacol Exp Ther. 2002;303(1):424-30.
Muratani, T., Minami, T., Enomoto, U., Sakai, M., Okuda-Ashitaka, E., Kiyokane, K., Mori, H., & Ito, S. (2002). Characterization of nociceptin/orphanin FQ-induced pain responses by the novel receptor antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride. The Journal of Pharmacology and Experimental Therapeutics, 303(1), 424-30.
Muratani T, et al. Characterization of Nociceptin/orphanin FQ-induced Pain Responses By the Novel Receptor Antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) Benzamide Monohydrochloride. J Pharmacol Exp Ther. 2002;303(1):424-30. PubMed PMID: 12235279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of nociceptin/orphanin FQ-induced pain responses by the novel receptor antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride. AU - Muratani,Tadatoshi, AU - Minami,Toshiaki, AU - Enomoto,Utako, AU - Sakai,Masato, AU - Okuda-Ashitaka,Emiko, AU - Kiyokane,Kimihiro, AU - Mori,Hidemaro, AU - Ito,Seiji, PY - 2002/9/18/pubmed PY - 2002/10/22/medline PY - 2002/9/18/entrez SP - 424 EP - 30 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 303 IS - 1 N2 - At the spinal level, nociceptin/orphanin FQ (Noc/OFQ) produces pronociceptive and allodynic effects at low doses (picogram range), while causing antinociceptive effects at high doses (microgram range). The discrepancy of pain modulation by Noc/OFQ at low and high doses raised a question whether Noc/OFQ exerted actions through the same Noc/OFQ receptor. In the present study, we examined the involvement of the Noc/OFQ receptor in pain responses with the novel nonpeptide antagonist N-(4-amino-2-methylquinolin-6-yl)-2-(4-ethylphenoxymethyl) benzamide monohydrochloride (JTC-801). Allodynia and hyperalgesia evoked by intrathecal administration of Noc/OFQ (50 pg/mouse) were dose dependently blocked by simultaneous administration of JTC-801 with IC(50) values of 32.2 and 363 pg, respectively. JTC-801 did not induce allodynia by itself. Subcutaneous injection of formalin into a hindpaw evoked biphasic pain behaviors such as flinching and biting in mice. Noc/OFQ at 10 pg increased the second-phase pain behaviors evoked by 1% formalin, whereas it strongly inhibited both the first-phase and second-phase pain evoked by 2% formalin at 1 microg. Although the pronociceptive effect by 10 pg of Noc/OFQ was dose dependently blocked by JTC-801 with an IC(50) value of 4.58 pg, the antinociceptive effects by 1 microg of Noc/OFQ were not antagonized by JTC-801. Furthermore, both phases of 2% formalin-induced pain behaviors were relieved by JTC-801. These results demonstrate that pronociceptive responses induced by a low dose of Noc/OFQ may be mediated through the Noc/OFQ receptor in the spinal cord and that JTC-801 can be a useful antagonist to examine the involvement of endogenous Noc/OFQ and mediation of the Noc/OFQ receptor under physiological and pathophysiological conditions including pain. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12235279/Characterization_of_nociceptin/orphanin_FQ_induced_pain_responses_by_the_novel_receptor_antagonist_N__4_amino_2_methylquinolin_6_yl__2__4_ethylphenoxymethyl__benzamide_monohydrochloride_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12235279 DB - PRIME DP - Unbound Medicine ER -