Disease relevance of N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide

• Oral administration of JTC-801 relieved the thermal hyperalgesia in neuropathic mice in a dose-dependent manner [1].

High impact information on N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide

• JTC-801 dose-dependently blocked the N/OFQ- and PGE(2)-induced allodynia, but not the PGF(2alpha)-induced one [2].
• Moreover, the inhibitory effect of N/OFQ was prevented by peptide ([Nphe(1)]N/OFQ(1-13)-NH(2) and UFP-101) and nonpeptide (J-113397 and JTC-801) NOP receptor selective antagonists [3].
• These results suggest that N/OFQ is involved in the maintenance of neuropathic pain and that the analgesic effect of JTC-801 on neuropathic pain is mediated by inhibition of NO production by neuronal NOS [1].
• In the present study, we studied the effect of JTC-801 on neuropathic pain induced by L5 spinal nerve transection in mice [1].
• 5 The time-dependency of JTC-801 action was studied in CHO cells expressing human NOP receptors [4].

Chemical compound and disease context of N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide

• Concerning hyperalgesia induced by formalin injection into the hindpaw, JTC-801 dose-dependently suppressed the second phase, but not the first phase, of the licking behavior [5].

Anatomical context of N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide

• JTC-801 inhibited the binding of [(3)H]-nociceptin to human ORL(1) receptors expressed in HeLa cells with a K(i) value of 44.5 nM [6].
• Although JTC-801 did not inhibit a CCI-induced decrease in BMC and BMD, it inhibited an increase in the number of osteoclasts in the JTC-801 groups [7].
• Furthermore, systemic JTC-801 reduced Fos-like immunoreactivity in the dorsal horn of the spinal cord (laminae I/II) [5].

Gene context of N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide

• Indeed, there is tremendous interest in the pharmaceutical industry in the development of nonpeptide ligands such as the potent ORL1 agonist, Ro 64-6198, as anxiolytics and the ORL1 antagonist JTC-801 as novel analgesics [8].
• However, a 21 min pre-application time was necessary for J-113397 and JTC-801 to prevent N/OFQ inhibition of [(3)H]-NE overflow [4].
• Pharmacological profiles of a novel opioid receptor-like1 (ORL(1)) receptor antagonist, JTC-801 [6].
• 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 [9].

Analytical, diagnostic and therapeutic context of N-(4-amino-2-methyl-6-quinolyl)-2-[(4-ethylphenoxy)methyl]benzamide

• This anti-nociceptive action of JTC-801 was not inhibited by naloxone (10 mg kg(-1), s.c.). We have demonstrated that JTC-801 antagonizes the ORL(1) receptor response, and that JTC-801 has efficacious and potent anti-nociceptive effects in acute pain animal models not only by intravenous injection but also oral administration [6].
• Tactile allodynia induced by L5/L6 spinal nerve ligation was reversed by both systemic (3-30 mg/kg) and spinal (22.5 and 45 pg) JTC-801 in a dose-dependent manner [5].
• We report that JTC-801 alleviates heat-evoked hyperalgesia and investigated the possible protective effect on osteoporosis induced by chronic constriction injury (CCI) in rats [7].

References