Desmopressin
Desmopressin is a synthetic vasopressin analog featuring a D-arginine substitution at position 8, functioning as a selective V2 receptor agonist used in the treatment of central diabetes insipidus.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C46H64N14O12S2 |
| Molecular Weight | 1069.23 g/mol |
| CAS Number | 62288-83-9 |
| IUPAC Name | (2S)-1-[(2S)-2-[[(4R,7S,10S,13S)-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-[(2S)-butan-2-yl]-6,9-dioxo-1,2,4,5,8,11-hexaoxocyclotridecane-4-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carboxamide |
| Peptide Class | Nonapeptide |
| Amino Acid Sequence | Cys-Tyr-Phe-Gln-Asn-Cys-Pro-DArg-Gly-NH2 (with disulfide bridge) |
Structure
Desmopressin (1-deamino-8-D-arginine vasopressin, dDAVP) is a synthetic analog of arginine vasopressin (AVP). It incorporates two modifications to the native nonapeptide:
-
Deamination at position 1: Removal of the N-terminal amino group from cysteine reduces susceptibility to aminopeptidase degradation.
-
D-Arginine at position 8: Substitution of L-arginine with the D-enantiomer at position 8 dramatically increases V2 receptor selectivity over V1a and V1b receptors, while also enhancing proteolytic stability.
The disulfide bridge between Cys1 and Cys6 forms a six-membered ring structure critical for biological activity.
V2 Receptor Selectivity
Desmopressin exhibits approximately 3000-fold selectivity for the V2 receptor over the V1a receptor, compared to a 30-fold selectivity ratio for native vasopressin. This selectivity profile minimizes pressor effects (V1a-mediated vasoconstriction) while maximizing antidiuretic activity.
At the V2 receptor in renal collecting duct principal cells, desmopressin stimulates aquaporin-2 (AQP2) trafficking to the apical membrane, increasing water permeability and reabsorption.
Clinical Applications
Desmopressin is the first-line treatment for central diabetes insipidus, where it replaces deficient endogenous vasopressin. It is also used for nocturnal enuresis, primary nocturnal enuresis, and von Willebrand disease (type 1), where it stimulates endothelial release of von Willebrand factor.
References
- Bichet, D.G., Knepper, M.A., & Bhatt, S. (2024). European Journal of Pharmacology. DOI: 10.1016/j.ejpharm.2023.175950
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