Knockout and pharmacological studies demonstrated that the activation of delta opioid peptide (DOP) receptors produces antidepressant-like effects in rodents. Here we report the results obtained with the novel DOP ligand H-Dmt-Tic-NH-CH2-Bid (UFP-502). UFP-502 bound with high affinity (pKi 9.43) to recombinant DOP receptors displaying moderate selectivity over MOP and KOP. In CHOhDOP [35S]GTPgS binding and mouse vas deferens experiments, UFP-502 behaved as a potent (pEC50 10.09 and 10.70, respectively) full agonist. In these preparations, naloxone, naltrindole and N,N(CH3)2Dmt-Tic-OH showed similar pA2 values against UFP-502 and DPDPE and the same rank order of potency. In vivo in mice, UFP- 502 mimicked DPDPE actions, producing a significant reduction of immobility time after intracerebroventricular administration in the forced swimming test and a clear antinociceptive effect after intrathecal injection in the tail withdrawal assay. However, while the effects of DPDPE were fully prevented by naltrindole those evoked by UFP-502 were unaffected (tail withdrawal assay) or only partially reversed (forced swimming test). In conclusion, UFP-502 represents a novel and useful chemical template for the design of selective agonists for the DOP receptor.

Dmt-Tic-NH-CH2-Bid (UFP-502), a potent DOP receptor agonist: In vitro and in vivo studies

VERGURA, Raffaella;GAVIOLI, Elaine Cristina;SPAGNOLO, Barbara;SALVADORI, Severo;REGOLI, Domenico;CALO', Girolamo
2006

Abstract

Knockout and pharmacological studies demonstrated that the activation of delta opioid peptide (DOP) receptors produces antidepressant-like effects in rodents. Here we report the results obtained with the novel DOP ligand H-Dmt-Tic-NH-CH2-Bid (UFP-502). UFP-502 bound with high affinity (pKi 9.43) to recombinant DOP receptors displaying moderate selectivity over MOP and KOP. In CHOhDOP [35S]GTPgS binding and mouse vas deferens experiments, UFP-502 behaved as a potent (pEC50 10.09 and 10.70, respectively) full agonist. In these preparations, naloxone, naltrindole and N,N(CH3)2Dmt-Tic-OH showed similar pA2 values against UFP-502 and DPDPE and the same rank order of potency. In vivo in mice, UFP- 502 mimicked DPDPE actions, producing a significant reduction of immobility time after intracerebroventricular administration in the forced swimming test and a clear antinociceptive effect after intrathecal injection in the tail withdrawal assay. However, while the effects of DPDPE were fully prevented by naltrindole those evoked by UFP-502 were unaffected (tail withdrawal assay) or only partially reversed (forced swimming test). In conclusion, UFP-502 represents a novel and useful chemical template for the design of selective agonists for the DOP receptor.
2006
Vergura, Raffaella; Valenti, E; Hebbes, Cp; Gavioli, Elaine Cristina; Spagnolo, Barbara; Mcdonald, J; Lambert, Dg; Balboni, G; Salvadori, Severo; Rego...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/471505
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