The present invention provides novel nucleoside and nucleotide derivatives that are useful agonists or antagonists of P1 or P2 receptors. For example, the present invention provides a compound of formula A-M, wherein A is modified adenine or uracil and M is a constrained cycloalkyl group. The adenine or uracil is bonded to the constrained cycloakyl group. The compounds of the present invention are useful in the treatment or prevention of various diseases including airway diseases (through A.sub.2B, A.sub.3, P2Y.sub.2 receptors), cancer (through A.sub.3, P2 receptors), cardiac arrhythmias (through A.sub.1 receptors), cardiac ischemia (through A.sub.1, A.sub.3 receptors), epilepsy (through A.sub.1, P2X receptors), and Huntington's Disease (through A.sub.2A receptors).