Dmt-Tic-NH-CH2-Bid (UFP-502), a potent DOP receptor agonist: In vitro and in vivo studies
| Autor: | Barbara Spagnolo, Elaine C. Gavioli, Raffaella Vergura, David G. Lambert, Elena Valenti, Gianfranco Balboni, John McDonald, Severo Salvadori, Christopher P. Hebbes, Domenico Regoli, Girolamo Calo |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Agonist
Male medicine.medical_specialty Opioids Delta opioid peptide receptor UFP-502 Receptor binding Bioassay Forced swimming and tail withdrawal assays Mice Physiology medicine.drug_class (+)-Naloxone CHO Cells Biology Biochemistry Cellular and Molecular Neuroscience Endocrinology Cricetulus In vivo Naltrindole Internal medicine Cricetinae Receptors Opioid delta medicine Animals Humans Receptor Opioid peptide Dipeptides Ligand (biochemistry) Benzimidazoles Behavioural despair test medicine.drug |
| Popis: | 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-CH 2 -Bid (UFP-502). UFP-502 bound with high affinity (p K i 9.43) to recombinant DOP receptors displaying moderate selectivity over MOP and KOP. In CHO hDOP [ 35 S]GTPγS binding and mouse vas deferens experiments, UFP-502 behaved as a potent (pEC 50 10.09 and 10.70, respectively) full agonist. In these preparations, naloxone, naltrindole and N , N (CH 3 ) 2 Dmt-Tic-OH showed similar p A 2 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. |
| Databáze: | OpenAIRE |
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