Investigational vasopressin receptor modulators in the pipeline

Expert Opinion on Investigational Drugs

Volumn 18, Issue 8, 2009, Pages 1119-1131

  Favory, Raphaël ^a   Salgado, Diamantino R ^a   Vincent, Jean Louis ^a  

^a ERASME HOSPITAL   (Belgium)

Author keywords

Terlipressin; Tolvaptan; Vasopressin; Vasopressin receptor agonist; Vasopressin receptor antagonist

Indexed keywords

1 [5 CHLORO 1 (2,4 DIMETHOXYLPHENYLSULFONYL) 2,3 DIHYDRO 3 (2 METHOXYPHENYL) 2 OXO 1H INDOL 3 YL] 4 HYDROXY N,N DIMETHYL 2 PYRROLIDINECARBOXAMIDE; ACETYLSALICYLIC ACID; ADRENALIN; ALBUMIN; ARGIPRESSIN; CONIVAPTAN; DESMOPRESSIN; HEPARIN; HYDROCORTISONE; LIXIVAPTAN; LYPRESSIN; MOZAVAPTAN; NITRIC OXIDE; NORADRENALIN; OXYTOCIN RECEPTOR; POTASSIUM CHANNEL; PURINERGIC P2 RECEPTOR; RELCOVAPTAN; SATAVAPTAN; TERLIPRESSIN; TICLOPIDINE; TOLVAPTAN; VASOPRESSIN; VASOPRESSIN RECEPTOR ANTAGONIST; VASOPRESSIN V1 RECEPTOR; VASOPRESSIN V2 RECEPTOR; VASOPRESSIN V3 RECEPTOR;

ABDOMINAL CRAMP; ARTERIAL PRESSURE; ARTERY THROMBOSIS; BERNARD SOULIER DISEASE; BLEEDING; BLEEDING DISORDER; BLEEDING TIME; BLOOD CLOTTING FACTOR 11 DEFICIENCY; BOLUS INJECTION; BRAIN VASOSPASM; CARDIOGENIC SHOCK; CARDIOPULMONARY INSUFFICIENCY; CONTINUOUS INFUSION; CORONARY ARTERY BLOOD FLOW; DEPRESSION; DIARRHEA; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG INTERMITTENT THERAPY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TARGETING; DYSMENORRHEA; EHLERS DANLOS SYNDROME; ESOPHAGUS HEMORRHAGE; FLUSHING; GENE LOCATION; HEADACHE; HEART ARREST; HEART ARRHYTHMIA; HEART FAILURE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HEMOPHILIA A; HEMOPTYSIS; HEPATORENAL SYNDROME; HORMONE ACTION; HUMAN; HYPERKALEMIA; HYPERNATREMIA; HYPOKALEMIA; HYPONATREMIA; INAPPROPRIATE VASOPRESSIN SECRETION; INTESTINE ISCHEMIA; KIDNEY POLYCYSTIC DISEASE; LOW DRUG DOSE; MARFAN SYNDROME; MAY HEGGLIN ANOMALY; NEUROGENIC DIABETES INSIPIDUS; NONHUMAN; OCULAR ALBINISM; ORTHOSTATIC HYPOTENSION; PARTIAL THROMBOPLASTIN TIME; PERIPHERAL EDEMA; POLLAKISURIA; PREMATURE LABOR; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RAYNAUD PHENOMENON; REVIEW; SEIZURE; SEPTIC SHOCK; SIDE EFFECT; SKIN DEFECT; STROKE; TACHYCARDIA; TACHYPHYLAXIS; THIRST; VEIN THROMBOSIS; VOMITING; VON WILLEBRAND DISEASE; XEROSTOMIA;

ANIMALS; BRAIN DISEASES; CARDIOVASCULAR DISEASES; CLINICAL TRIALS AS TOPIC; DRUGS, INVESTIGATIONAL; HEMORRHAGE; HUMANS; INAPPROPRIATE ADH SYNDROME; RECEPTORS, VASOPRESSIN; SKIN DISEASES; VASOPRESSINS;

EID: 68049120588     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543780903066764     Document Type: Review

References (104)

1. Oliver G, Schäfer EA. On the physiological action of extract of pituitary body and certain other glandular organs. J Physiol 1895;18:277-9
2. Vincent JL, Su F. Physiology and pathophysiology of the vasopressinergic system. Best Pract Res Clin Anaesthesiol 2008;22:243-52
3. Fabian M, Forsling ML, Jones JJ, et al. The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability. J Physiol 1969;204:653-68
4. Lange M, Ertmer C, Westphal M. Vasopressin vs. terlipressin in the treatment of cardiovascular failure in sepsis. Intensive Care Med 2008;34:821-32 •• A comprehensive review of vasopressin and terlipressin pharmacology and use in the context of septic shock.
5. Knepper MA, Inoue T. Regulation of aquaporin-2 water channel trafficking by vasopressin. Curr Opin Cell Biol 1997;9:560-4
6. Antunes-Rodrigues J, de Castro M, Elias LL, et al. Neuroendocrine control of body fluid metabolism. Physiol Rev 2004;84:169-208
7. Lee B, Yang C, Chen TH, et al. Effect of AVP and oxytocin on insulin release: involvement of V1b receptors. Am J Physiol 1995;269:E1095-100
8. Zenteno-Savin T, Sada-Ovalle I, Ceballos G, et al. Effects of arginine vasopressin in the heart are mediated by specific intravascular endothelial receptors. Eur J Pharmacol 2000;410:15-23
9. Forsling ML, Aziz LA, Miller M, et al. Conversion of triglycylvasopressin to lysine-vasopressin in man. J Endocrinol 1980;85:237-44
10. Ryckwaert F, Virsolvy A, Fort A, et al. Terlipressin, a provasopressin drug exhibits direct vasoconstrictor properties: consequences on heart perfusion and performance. Crit Care Med 2009;37:876-81
11. Franchini M. The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol 2007;82:731-5 •• A very complete review.
12. Gross P. Treatment of hyponatremia. Intern Med 2008;47:885-91
13. Chugh SS, Reinier K, Teodorescu C, et al. Epidemiology of sudden cardiac death: clinical and research implications. Prog Cardiovasc Dis 2008;51:213-28
14. Lindner KH, Haak T, Keller A, et al. Release of endogenous vasopressors during and after cardiopulmonary resuscitation. Heart 1996;75:145-50
15. Ditchey RV, Lindenfeld J. Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs. Circulation 1988;78:382-9
16. Wenzel V, Lindner KH, Krismer AC, et al. Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs. J Am Coll Cardiol 2000;35:527-33
17. Prengel AW, Lindner KH, Keller A, et al. Cardiovascular function during the postresuscitation phase after cardiac arrest in pigs: a comparison of epinephrine versus vasopressin. Crit Care Med 1996;24:2014-9
18. Voelckel WG, Lindner KH, Wenzel V, et al. Effects of vasopressin and epinephrine on splanchnic blood flow and renal function during and after cardiopulmonary resuscitation in pigs. Crit Care Med 2000;28:1083-8
19. Popp E, Vogel P, Teschendorf P, et al. Vasopressors are essential during cardiopulmonary resuscitation in rats: Is vasopressin superior to adrenaline? Resuscitation 2007;72:137-44
20. Stroumpoulis K, Xanthos T, Rokas G, et al. Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental study. Crit Care 2008;12:R40
21. Lindner KH, Prengel AW, Brinkmann A, et al. Vasopressin administration in refractory cardiac arrest. Ann Intern Med 1996;124:1061-4
22. Lindner KH, Dirks B, Strohmenger HU, et al. Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997;349:535-7
23. Mayr V, Luckner G, Jochberger S, et al. Arginine vasopressin in advanced cardiovascular failure during the post-resuscitation phase after cardiac arrest. Resuscitation 2007;72:35-44
24. Stiell IG, Hebert PC, Wells GA, et al. Vasopressin versus epinephrine for in-hospital cardiac arrest: a randomised controlled trial. Lancet 2001;358:105-9
25. Wenzel V, Krismer AC, Arntz HR, et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350:105-13
26. Gueugniaud PY, David JS, Chanzy E, et al: Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med 2008;359:21-30 •• This RCT has sufficient power to conclude that addition of vasopressin to epinephrine is not beneficial in out-of-hospital cardiac arrest.
27. Kalra PR, Anker SD, Coats AJ. Water and sodium regulation in chronic heart failure: the role of natriuretic peptides and vasopressin. Cardiovasc Res 2001;51:495-509
28. Nakamura Y, Haneda T, Osaki J, et al. Hypertrophic growth of cultured neonatal rat heart cells mediated by vasopressin V(1A) receptor. Eur J Pharmacol 2000;391:39-48
29. Tahara A, Tomura Y, Wada K, et al. Effect of YM087, a potent nonpeptide vasopressin antagonist, on vasopressin-induced hyperplasia and hypertrophy of cultured vascular smooth-muscle cells. J Cardiovasc Pharmacol 1997;30:759-66
30. Goldsmith SR. The role of vasopressin in congestive heart failure. Cleve Clin J Med 2006;73(Suppl 3):S19-23
31. Gheorghiade M, Gattis WA, O'Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 2004;291:1963-71
32. Konstam MA, Gheorghiade M, Burnett JC, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 2007;297:1319-31
33. Goldsmith SR, Elkayam U, Haught WH, et al. Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated heart failure: a dose-ranging pilot study. J Card Fail 2008;14:641-7
34. Udelson JE, McGrew FA, Flores E, et al. Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction. J Am Coll Cardiol 2007;49:2151-9
35. Abraham WT, Shamshirsaz AA, McFann K, et al. Aquaretic effect of lixivaptan, an oral, non-peptide, selective V2 receptor vasopressin antagonist, in New York Heart Association functional class II and III chronic heart failure patients. J Am Coll Cardiol 2006;47:1615-21
36. Russell SD, Selaru P, Pyne DA, et al. Rationale for use of an exercise end point and design for the ADVANCE (A Dose Evaluation of a Vasopressin Antagonist in CHF Patients Undergoing Exercise) trial. Am Heart J 2003;145:179-86
37. Sharshar T, Blanchard A, Paillard M, et al. Circulating vasopressin levels in septic shock. Crit Care Med 2003;31:1752-8
38. Jochberger S, Dorler J, Luckner G, et al. The vasopressin and copeptin response to infection, severe sepsis, and septic shock. Crit Care Med 2009;37:476-82
39. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001;345:588-95 •• A very good review discussing the main mechanisms involved in the genesis of vasodilatory shock and the benefits of vasopressin therapy in this type of shock.
40. Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997;95:1122-5 •• The first study to demonstrate low vasopressin levels in patients with septic shock and to show that vasopressin administration was associated with improvement in arterial blood pressure in these patients.
41. Wakatsuki T, Nakaya Y, Inoue I. Vasopressin modulates K(+)-channel activities of cultured smooth muscle cells from porcine coronary artery. Am J Physiol 1992;263:H491-6
42. Umino T, Kusano E, Muto S, et al. AVP inhibits LPS- and IL-1beta-stimulated NO and cGMP via V1 receptor in cultured rat mesangial cells. Am J Physiol 1999;276:F433-41
43. Holmes CL, Walley KR. Arginine vasopressin in the treatment of vasodilatory septic shock. Best Pract Res Clin Anaesthesiol 2008;22:275-86 • Good review discussing the use of vasopressin in vasodilatory septic shock and the results of some recent RCTs.
44. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008;358:877-87 •• The largest clinical trial to date of vasopressin use in septic shock, demonstrating a lower mortality rate compared to norepinephrine in patients with less severe shock.
45. Gordon AC, Russell JA, Holmes Boulton CL, et al. The effect of vasopressin on acute renal failure in septic shock [abstract]. Am J Respir Crit Care Med 2007;175:A596
46. Russell JA, Walley KR, Gordon AC, et al. Interaction of vasopressin infusion, corticosteroid treatment, and mortality of septic shock. Crit Care Med 2009;37:811-8
47. O'Brien A, Clapp L, Singer M. Terlipressin for norepinephrine-resistant septic shock. Lancet 2002;359:1209-10
48. Asfar P, Hauser B, Ivanyi Z, et al. Low-dose terlipressin during long-term hyperdynamic porcine endotoxemia: effects on hepatosplanchnic perfusion, oxygen exchange, and metabolism. Crit Care Med 2005;33:373-80
49. Morelli A, Ertmer C, Lange M, et al. Continuous terlipressin versus vasopressin infusion in septic shock: the TERLIVAP study [abstract]. Crit Care 2008;12(Suppl 2):P403
50. Morelli A, Ertmer C, Westphal M. Terlipressin in the treatment of septic shock: the earlier the better? Best Pract Res Clin Anaesthesiol 2008;22:317-21
51. Federici AB, Mazurier C, Berntorp E, et al. Biologic response to desmopressin in patients with severe type 1 and type 2 von Willebrand disease: results of a multicenter European study. Blood 2004;103:2032-8
52. Lethagen S. Desmopressin in mild hemophilia A: indications, limitations, efficacy, and safety. Semin Thromb Hemost 2003;29:101-6
53. Ioannou GN, Doust J, Rockey DC. Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther 2003;17:53-64
54. de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol 2005;43:167-76
55. Ramon P, Wallaert B, Derollez M, et al. [Treatment of severe hemoptysis with terlipressin. Study of the efficacy and tolerance of this product]. Rev Mal Respir 1989;6:365-8
56. Pea L, Roda L, Boussaud V, et al. Desmopressin therapy for massive hemoptysis associated with severe leptospirosis. Am J Respir Crit Care Med 2003;167:726-8
57. Anwar D, Schaad N, Mazzocato C. Aerosolized vasopressin is a safe and effective treatment for mild to moderate recurrent hemoptysis in palliative care patients. J Pain Symptom Manage 2005;29:427-9
58. Mannucci PM, Vicente V, Vianello L, et al. Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood 1986;67:1148-53
59. Schulman S, Johnsson H. Heparin, DDAVP and the bleeding time. Thromb Haemost 1991;65:242-4
60. Salzman EW, Weinstein MJ, Weintraub RM, et al. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery: a double-blind randomized trial. N Engl J Med 1986;314:1402-6
61. Levi M, Cromheecke ME, de Jonge E, et al. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet 1999;354:1940-7
62. Del Tredici AL, Vanover KE, Knapp AE, et al. Identification of novel selective V2 receptor non-peptide agonists. Biochem Pharmacol 2008;76:1134-41
63. Delgado TJ, Arbab MA, Warberg J, et al. The role of vasopressin in acute cerebral vasospasm. Effect on spasm of a vasopressin antagonist or vasopressin antiserum. J Neurosurg 1988;68:266-73
64. Trandafir CC, Nishihashi T, Wang A, et al. Participation of vasopressin in the development of cerebral vasospasm in a rat model of subarachnoid haemorrhage. Clin Exp Pharmacol Physiol 2004;31:261-6
65. Steinwall M, Bossmar T, Gaud C, et al. Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women. Acta Obstet Gynecol Scand 2004;83:12-8
66. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967;42:790-806
67. Soupart A, Gross P, Legros JJ, et al. Successful long-term treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion with satavaptan (SR121463B), an orally active nonpeptide vasopressin V2-receptor antagonist. Clin J Am Soc Nephrol 2006;1:1154-60
68. Torres VE. Cyclic AMP, at the hub of the cystic cycle. Kidney Int 2004;66:1283-5
69. Gattone VH, Wang X, Harris PC, et al. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med 2003;9:1323-6 •• A pioneering study.
70. Torres VE, Wang X, Qian Q, et al. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med 2004;10:363-4
71. Wang X, Gattone V, Harris PC, et al. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat. J Am Soc Nephrol 2005;16:846-51
72. Krag A, Moller S, Henriksen JH, et al. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology 2007;46:1863-71
73. Martin-Llahi M, Pepin MN, Guevara M, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008;134:1352-9
74. Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci 2008;53:830-5
75. Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology 2008;134:1360-8
76. Krag A, Borup T, Moller S, et al. Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome. Adv Ther 2008;25:1105-40 • A detailed review on this topic.
77. Hayoz D, Bizzini G, Noel B, et al. Effect of SR 49059, a V1a vasopressin receptor antagonist, in Raynaud's phenomenon. Rheumatology (Oxford) 2000;39:1132-8
78. Brouard R, Bossmar T, Fournie-Lloret D, et al. Effect of SR49059, an orally active V1a vasopressin receptor antagonist, in the prevention of dysmenorrhoea. BJOG 2000;107:614-9
79. Steinwall M, Bossmar T, Brouard R, et al. The effect of relcovaptan (SR 49059), an orally active vasopressin V1a receptor antagonist, on uterine contractions in preterm labor. Gynecol Endocrinol 2005;20:104-9
80. Ouattara A, Landi M, Le Manach Y, et al. Comparative cardiac effects of terlipressin, vasopressin, and norepinephrine on an isolated perfused rabbit heart. Anesthesiology 2005;102:85-92
81. Westphal M, Freise H, Kehrel BE, et al. Arginine vasopressin compromises gut mucosal microcirculation in septic rats. Crit Care Med 2004;32:194-200
82. Sun Q, Dimopoulos G, Nguyen DN, et al. Low-dose vasopressin in the treatment of septic shock in sheep. Am J Respir Crit Care Med 2003;168:481-6
83. Asfar P, Pierrot M, Veal N, et al. Low-dose terlipressin improves systemic and splanchnic hemodynamics in fluid-challenged endotoxic rats. Crit Care Med 2003;31:215-20
84. Morelli A, Ertmer C, Lange M, et al. Effects of short-term simultaneous infusion of dobutamine and terlipressin in patients with septic shock: the DOBUPRESS study. Br J Anaesth 2008;100:494-503
85. Rehberg S, Ertmer C, Kohler G, et al. Role of arginine vasopressin and terlipressin as first-line vasopressor agents in fulminant ovine septic shock. Intensive Care Med 2009 (In Press)
86. Baker CH, Sutton ET, Zhou Z, et al. Microvascular vasopressin effects during endotoxin shock in the rat. Circ Shock 1990;30:81-95
87. Hollenberg SM, Tangora JJ, Piotrowski MJ, et al. Impaired microvascular vasoconstrictive responses to vasopressin in septic rats. Crit Care Med 1997;25:869-73
88. Vanner S, Jiang MM, Brooks VL, et al. Characterization of vasopressin actions in isolated submucosal arterioles of the intestinal microcirculation. Circ Res 1990;67:1017-26
89. Hiltebrand LB, Krejci V, Jakob SM, et al. Effects of vasopressin on microcirculatory blood flow in the gastrointestinal tract in anesthetized pigs in septic shock. Anesthesiology 2007;106:1156-67
90. Knotzer H, Maier S, Dunser MW, et al. Arginine vasopressin does not alter mucosal tissue oxygen tension and oxygen supply in an acute endotoxemic pig model. Intensive Care Med 2006;32:170-4
91. Knotzer H, Pajk W, Maier S, et al. Arginine vasopressin reduces intestinal oxygen supply and mucosal tissue oxygen tension. Am J Physiol Heart Circ Physiol 2005;289:H168-73
92. Malay MB, Ashton JL, Dahl K, et al. Heterogeneity of the vasoconstrictor effect of vasopressin in septic shock. Crit Care Med 2004;32:1327-31
93. Nakajima Y, Baudry N, Duranteau J, et al. Effects of vasopressin, norepinephrine, and L-arginine on intestinal microcirculation in endotoxemia. Crit Care Med 2006;34:1752-7
94. Kiszka-Kanowitz M, Henriksen JH, Hansen EF, et al. Effect of terlipressin on blood volume distribution in patients with cirrhosis. Scand J Gastroenterol 2004;39:486-92
95. Ristagno G, Sun S, Tang W, et al. Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. Crit Care Med 2007;35:2145-9
96. Boerma EC, van der Voort PH, Ince C. Sublingual microcirculatory flow is impaired by the vasopressin-analogue terlipressin in a patient with catecholamine-resistant septic shock. Acta Anaesthesiol Scand 2005;49:1387-90
97. Dubois MJ, De Backer D, Creteur J, et al. Effect of vasopressin on sublingual microcirculation in a patient with distributive shock. Intensive Care Med 2003;29:1020-3
98. Luckner G, Dunser MW, Stadlbauer KH, et al. Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome [abstract]. Crit Care 2006;10:R40
99. Escorsell A, Ruiz DA, Planas R, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology 2000;32:471-6
100. Dunwoodie E, Jowett S. Terlipressin causing a hyponatraemic seizure. Scand J Gastroenterol 2007;42:665
101. Stephan F, Paillard F. Terlipressin-exacerbated hypokalaemia. Lancet 1998;351:1249-50
102. Mannucci PM, Lusher JM. Desmopressin and thrombosis. Lancet 1989;2:675-6
103. Franchini M, Krampera M, Veneri D. Deep vein thrombosis after orthopedic surgery in a patient with type 1 von Willebrand disease and mutations in the MTHFR and beta-fibrinogen genes. Thromb Haemost 2003;90:963-4
104. Lemmens-Gruber R, Kamyar M. Vasopressin antagonists. Cell Mol Life Sci 2006;63:1766-79 •• A good review on this topic.