Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)NH2 analogues. 2. In vivo studies.

As part of a structure-activity study focused on the Phe(4) residue of nociceptin (NC) (1-13)NH(2), we identified two highly potent and selective agonists for the OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2), whose in vitro pharmacological profiles have been described in the companion paper. In the present study, we investigated the actions of [(pF)Phe(4)]NC(1-13)NH(2) and compared it with those of NC(1-13)NH(2) in a battery of vivo assays. In the locomotor activity test in mice, 1 nmol NC(1-13)NH(2) given intracerebroventricularly (i.

Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)amide analogues. 1. In vitro studies.

Phe(4) in the nociceptin (NC) sequence has been identified as the most critical residue for receptor interaction. In the present study, we investigated the pharmacological activity of a series of NC(1-13)NH(2) analogues, in which the hydrogen atom in the para position of Phe(4) was substituted with F, NO(2), CN, Cl, Br, I, CH(3), OH or NH(2). In receptor binding studies, performed using CHO cells expressing the recombinant human NC receptor (CHO(hOP4)) and in rat cerebral cortex membranes, [(pF)Phe(4)]NC(1-13)NH(2), [(pNO(2))Phe(4)]NC(1-13)NH(2), and [(pCN)Phe(4)]NC(1-13)NH(2) displayed higher affinity than NC(1-13)NH(2).

[Nphe1,Arg14,Lys15]nociceptin-NH2, a novel potent and selective antagonist of the nociceptin/orphanin FQ receptor.

1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor.

Pharmacological profile of nociceptin/orphanin FQ receptors.

1. Nociceptin/orphanin FQ (NC) and its receptor (OP4) represent a novel peptide/receptor system pharmacologically distinct from classical opioid systems. 2.

[Arg(14),Lys(15)]nociceptin, a highly potent agonist of the nociceptin/orphanin FQ receptor: in vitro and in vivo studies.

The nociceptin (NC)/orphanin FQ analog, [Arg(14),Lys(15)]NC, has been recently demonstrated to behave as a potent agonist at the human recombinant NC receptors (OP(4)). In this study, we evaluated the pharmacological profile of [Arg(14),Lys(15)]NC in vitro on the native OP(4) receptors expressed in isolated tissues and in vivo in the locomotor activity and the tail-withdrawal assays in mice. On isolated tissues, [Arg(14),Lys(15)]NC mimicked the effects of NC, showing similar maximal effects but higher potencies (17-fold in the mouse vas deferens, 10-fold in the rat vas deferens, and about 5-fold in the guinea pig ileum and mouse colon).