1. VASOPRESSIN RECEPTOR
ANTAGONISTS AND IT’S THERAPEUTIC
POTENTIAL
Dr Amit mittal
Tutor
Department of Pharmacology
LLRM Medical College,Meerut

2. Vasopressin(Antidiuretic hormone)
 A nonapeptide hormone
 Mammalian ADH-8 Arginine vasopressin(AVP)
 Synthesized in hypothalamus and transported
to the posterior pituitary where it is stored

4. ACTIONS OF ADH-
 KIDNEY-act on CD and increase water permeability
 BLOOD VESSEL-cause vasoconstriction
 CNS-regulation of temperature,ACTHrelease,tasks
learning
 Visceral smooth muscle contraction
 Increased peristalsis in gut
 Induce platelet aggregation
 Cause hepatic glycogenolysis
 Release coagulation factor Vlll and von
Willebrands’factor from vascular endothelium

5. Stimuli for ADH secretion
 Hypovolaemia
 Hyperosmolarity
 Pain,Stress,Anxiety,Nausea
 Drugs
 Acetylcholine
 Nicotine
 Morphine
 Indomethacin
 Histamine
 Prostaglandins
 Chlorpropamide
 Carbamazepine
 General Anaesthetics

6. Some chronic conditions
 CHF
 Cirrhosis
 Prolonged use of diuretics
Inhibition of ADH
 Ethanol
 Phenytoin
 Glucocorticoids
 GABA
 ANP

7. • REGULATION OF OSMOLARITY OF
EXTRACELLULAR FLUID

13. Vasopressin Receptors
 G Protein Coupled Cell Membrane
Receptor
 Three types
 V1a
 V1b(V3)
 V2

15. VASOPRESSIN RECEPTOR
ANTAGONIST-
 Peptide group
 Non-Peptide group
 CONIVAPTAN
 TOLVAPTAN
 LIXIVAPTAN
 RELCOVAPTAN
 SSR-149414
 SATAVAPTAN
 MOZAVAPTAN

16. CONIVAPTAN-
 Non selective (V2+V1a)
 IV formulation only
 Euvolaemic and Hypervolaemic Hyponatraemia
 Acute heart failure with hyponatraemia
 Cirrhosis with ascites
 Nephrotic syndrome
TOLVAPTAN-
 V2 selective
 Oral
 Used in hyponatraemia due to Congestive heart
failure,Cirrhosis,SIADH
 Dose-15-45mg/day
LIXIVAPTAN-
 V2 selective
 Oral

17. DRUGS UNDER CLINICAL TRIAL
RELCOVAPTAN-
 V1a selective
 Raynaud’s disease
 Dysmenorrhea
 Tocolytic
SSR-149415-
 V1b selective
 Psychiatric disorder
SATAVAPTAN (V2 selective)
MOZAVAPTAN

18. S/E-
 Dry mouth
 Constipation
 Polyuria
 Polydipsia
 Fever
 Postural hypotension
 Weakness