薬物疫学と医薬品の安全性の進歩

概要

The Tolvaptan Role on Acth Secretion and its Potential Therapeutic Implications

Ermira Cuka

Tolvaptan is an oral arginine vasopressin (AVP) receptor, antagonist. Due to its aquaretic properties, tolvaptan is indicated in the treatment of congestive heart failure, cirrhosis of the liver, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and autosomal dominant polycystic kidney disease (ADPKD). Studies in Cushing's disease and clinical observation in a patient with palmar hyperhidrosis dictate a tolvaptan role in the central nervous system (CNS) mainly through adrenocorticotropic hormone (ACTH) suppression. AVP receptors have a wide distribution in the body, including the CNS. Centrally AVP stimulates ACTH secretion by corticotrope cells which express all three vasopressin receptors (V1, V2 and, V3). ACTH is involved in both cortisol secretion and sympathetic nervous system activation. Cushing's disease is caused by prolonged exposure to high cortisol levels engendered by tumors of the pituitary gland secreting ACTH. Palmar hyperhidrosis is a chronic neurologic disorder characterized by excessive sweating of eccrine glands, which worsens during stress. An excessive response of CNS to physiologic stress constitutes the most common etiopathogenetic hypothesis of palmar hyperhidrosis. The current article's data are collateral evidence, emerged from studies that had other study objectives. The tolvaptan role in these diseases probably is sustained by aberrant or overexpression of AVP receptors in corticotrope cells. The physiopathology of tolvaptan action on the central nervous system is reported. An aimed research to evaluate the effect of tolvaptan in both Cushing's syndrome and palmar hyperhidrosis is needed.