3 The Chemistry of Guanidines and their Actions at Adrenergic Nerve Endings

Abstract

Publisher Summary This chapter tells us that guanidines have been studied for many years as a possible source of medically useful compounds, but the recent vast increase in the literature on guanidine derivatives stems principally from the discovery of the potent hypotensive properties of guanethidine. The short-lived use of synthalin as a hypoglycaemic drug led to numerous studies on guanidines as potential insulin substitutes. Synthalin itself was withdrawn when it was reported that it can cause liver damage, and the widespread interest in guanidines eventually lapsed. The chapter also reveals that synthetic guanidine derivatives have been used successfully in the treatment of a variety of diseases, but the major success has undoubtedly been their exploitation as antihypertensive drugs. The chapter explains that all the drugs appear to lower blood pressure by blockade of sympathetic nerves. The structure, physical properties, and synthesis of guanidines are summarized and the methods used for testing these drugs are outlined. The relationships between structure and adrenergic neurone blockade are discussed. The relevant biochemical effects connected with these pharmacological actions are surveyed, with particular reference to possible mechanisms of action. The chapter also reviews the biochemistry of guanethidine with particular emphasis on tissue distribution and metabolism.