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Chapter 6 Advances in Vasopressin Receptor Agonists and Antagonists

2009; Elsevier BV; Linguagem: Inglês

10.1016/s0065-7743(09)04406-6

1557-8437

Thomas Ryckmans,

Stress Responses and Cortisol

Publisher Summary This chapter discusses the recent advances in the development of non-peptidic vasopressin receptor ligands, focusing on new series, structure–activity relationship (SAR), and preclinical data. Arginine vasopressin (AVP) is a 9–amino-acid cyclic peptide that exerts its effect through the V1a, V1b, V2, and oxytocin (OT) family of G-protein- coupled receptors (GPCRs). There is growing evidence that AVP, through its action at V1a and V1b receptors, is involved in the modulation of several higher brain functions such as response to stress, mood, memory formation, aggressivity, and sociality. The chapter examines V2 receptor antagonists and agonists for the modulation of renal function and cardiovascular conditions. V1a receptor antagonists are being actively investigated for indications such as dysmenorrhea, given the unmet medical need and the large patient population. On the contrary, the involvement of the V1a and V1b receptors in depression, anxiety and stress disorders has been clearly demonstrated in preclinical models. However, the discovery of an orally bioavailable, well-tolerated, and central nervous system (CNS)-penetrant antagonist of these receptors is still a challenge.