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Yale J Biol Med. 1978 Nov–Dec; 51(6): 605–614. | PMCID: PMC2595600 |
An Early Look at the Therapeutic Uses of Some New Vasopressin Analogs in Gastroenterology 1Joseph H. Cort and Irving L. Schwartz Abstract Natural vasopressins have been used, with varying success, in attempts to stop bleeding from esophageal varices for over two decades. Reasons for lack of success include (a) failure to induce a sufficiently prolonged and constant vasoconstrictor effect at the bleeding site, (b) dangerous side-effects, and (c) release of plasminogen activator induced by the peptides which can lyse any clot as it forms. In the last decade analogs of vasopressin have been developed with a prolonged action, using two separate principles of chemical modification: (1) hormonogens, and (2) blockage of sites of inactivating enzymatic cleavage (in particular “carba” analogs without a disulfide bridge). These two categories of analog are compared here: the carba analogs have the advantages of high potency (higher than the parent hormone) with prolongation, but are also very active on the plasminogen activator release system. The hormonogens combine prolongation with low potency, but have lost not only a releasing action on plasminogen activator, but also, by virtue of altered release kinetics, have effectively lost cardiovascular toxicity. Mechanisms of analog action and receptor interaction are presented, along with initial clinical experiences. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References. Images in this article Click on the image to see a larger version. These references are in PubMed. This may not be the complete list of references from this article. - KEHNE JH, HUGHES FA, GOMPERTZ ML. The use of surgical pituitrin in the control of esophageal varix bleeding; an experimental study and report of two cases. Surgery. 1956 Jun;39(6):917–925. [PubMed]
- SAPIRSTEIN LA. Regional blood flow by fractional distribution of indicators. Am J Physiol. 1958 Apr;193(1):161–168. [PubMed]
- Cort JH, Albrecht I, Nováková J, Mulder JL, Jost K. Regional and systemic haemodynamic effects of some vasopressins: structural features of the hormone which prolong activity. Eur J Clin Invest. 1975 Apr;5(2):165–175. [PubMed]
- Cort JH, Jeanjean MF, Thomson AE, Nickerson M. Effects of "hormonogen" forms of neurohypophysial peptides in hemorrhagic shock in dogs. Am J Physiol. 1968 Mar;214(3):455–462. [PubMed]
- Vosmík J, Jedlicka K, Mulder JL, Cort JH. Action of the triglycyl hormonogen of vasopressin (glypressin) in patients with liver cirrhosis and bleeding esophageal varices. Gastroenterology. 1977 Apr;72(4 Pt 1):605–609. [PubMed]
- Cash JD, Gader AM, Mulder JL, Cort JH. Structure--activity relations of the fibrinolytic response to vasopressins in man. Clin Sci Mol Med. 1978 Apr;54(4):403–409. [PubMed]
- HUGUENIN RL, STUERMER E, BOISSONNAS RA, BERDE B. (DESAMINO-ARGININE-VASOPRESSIN, AN ANALOGUE OF ARGININE-VASOPRESSIN WITH HIGH ANTIDIURETIC ACTIVITY.). Experientia. 1965 Feb 15;21:68–69. [PubMed]
- Kyncl J, Rezábek K, Kasafírek E, Pliska V, Rudinger J. 'Hormonogen' analogues of lysine vasopressin: rat pressor and antidiuretic activities. Eur J Pharmacol. 1974 Oct;28(2):294–301. [PubMed]
- Pliska V, Chard T, Rudinger J, Forsling ML. In vivo activation of synthetic hormonogens of lysine vasopressin: Na-glycyl-glycyl-glycyl-[8-lysine]vassopressin in the cat. Acta Endocrinol (Copenh). 1976 Mar;81(3):474–481. [PubMed]
- Sjöquist PO, Bjellin L, Carter AM. Effect of a vasopressin analogue (Nalpha-glycyl-glycyl-glycyl-[8-lysine]-vasopressin) on organ blood flow in the pregnant guinea pig. Acta Pharmacol Toxicol (Copenh). 1977 Mar;40(3):369–377. [PubMed]
- Akerlund M, Andersson KE. Vasopressin response and terbutaline inhibition of the uterus. Obstet Gynecol. 1976 Nov;48(5):528–536. [PubMed]
- Conn HO, Ramsby GR, Storer EH, Mutchnick MG, Joshi PH, Phillips MM, Cohen GA, Fields GN, Petroski D. Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial. Gastroenterology. 1975 Feb;68(2):211–221. [PubMed]
- SHALDON S, SHERLOCK S. The use of vasopressin ('pitressin') in the control of bleeding from oesophageal varices. Lancet. 1960 Jul 30;2(7144):222–225. [PubMed]
- Aronsen KF, Wetterlin S, Emas S, Vojtsek V, Mulder JL, Cort JH. Die Wirkung von Triglycyl-Lysin-Vasopressin auf Kontrollpersonen und Patienten mit Blutungen des oberen Gastrointestinaltraktes. Klin Wochenschr. 1975 Aug 15;53(16):747–753. [PubMed]
- Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. Lancet. 1977 Apr 23;1(8017):869–872. [PubMed]
- Cobb WE, Spare S, Reichlin S. Neurogenic diabetes insipidus: management with dDAVP (1-desamino-8-D arginine vasopressin). Ann Intern Med. 1978 Feb;88(2):183–188. [PubMed]
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