Analogues of Arginine Vasopressin Modified in Position 2 or 3 with Naphthylalanine: Selective Antagonists of Oxytocin In-vitro
| Autor: | M Sobocińska, Marcin Janecki, Izabela Derdowska, Henryk I. Trzeciak, Ewa Konieczna, J Janecka, E Lempicka, W Kozik, Samed Melhem, Bernard Lammek |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Vasopressin Tocolytic agent medicine.medical_specialty Arginine Pharmaceutical Science Peptide Uterotonic In Vitro Techniques Oxytocin Structure-Activity Relationship chemistry.chemical_compound Internal medicine medicine Peptide synthesis Animals Rats Wistar Pharmacology chemistry.chemical_classification Uterus Antagonist Diuresis Rats Arginine Vasopressin Endocrinology chemistry Female hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Pharmacy and Pharmacology. 52:1105-1112 |
| ISSN: | 2042-7158 0022-3573 |
| Popis: | In this study we describe the synthesis and some pharmacological properties of six new analogues of arginine vasopressin (AVP). Five of the peptides were substituted in position 2 with L-1-naphthylalanine (L-1-Nal) or D-1-naphthylalanine (D-1-Nal); one had D-1-Nal in position 3. All analogues were tested in bioassays for pressor and antidiuretic activity. We also tested the uterotonic activity of the peptides in-vitro. Two of the new peptides were moderately potent V1a and oxytocin antagonists. The modifications proposed resulted in a drop or the removal of antidiuretic activity and in the removal of pressor activity, or conversion into moderate antagonists. Two peptides ([Mpa1, (L-1-Nal)2]AVP and [Mpa1, (D-1-Nal)2]AVP) which appear not to interact with V1a and V2 receptors were exceptionally selective oxytocin antagonists in-vitro. These compounds with selective oxytocin antagonistic activity may be promising candidates for the development of potential tocolytic agents for the prevention of pre-term labour. |
| Databáze: | OpenAIRE |
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