Chapter 3 - Medicinal Chemistry of Adenosine Receptors in Brain and Periphery

Abstract

This chapter discusses the fact that there are different types of receptors which help to regulate the intracellular signaling system in various ways. On the basis of both pharmacological and biochemical studies, these receptors have been usually divided into four subtypes such as adenosine A1, A2A, A2B, and A3 receptors. These receptors generally belong to the family of receptors coupled to G-proteins. The thoroughly investigated subtypes are the high-affinity A1 and A2A receptors, both of which are activated by adenosine in low, nanomolar, or at least submicromolar concentrations, depending on the cell system investigated. This chapter also reviews the two promising areas where A1 antagonists may be therapeutic. These are cognitive deficit and acute renal failure. Selective adenosine A2A antagonists such as KW-6002 provide new possibilities for the treatment of Parkinson's disease. Noteworthy progress has been made with the synthesis of new compounds, such as 8-styrylxanthines and new nonxanthine heterocycles. Theophylline, the nonselective adenosine antagonist, has been shown to improve motor scores and the mental state of parkinsonian patients.