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Potassium channels constitute the largest and most ubiquitous and diverse ion channel family. They regulate several physiological processes including electrical signalling, hormone and neurotransmitter release, muscle contraction, cardiac function, cell proliferation and immune function, which are underscored by the association of K+ channel mutations to numerous inherited diseases. Although many challenges remain unsolved, the availability of diverse expression systems, molecular cloning and genetic linkage analysis has led to the upgradation of available topological data, identification of disease-producing loci, and better understanding of mutation-linked channelopathies. Moreover, in 2016, a new nomenclature (KNa1.1 for KCa4.1, and KNa1.2 for KCa4.2) has been assigned and implemented in the IUPHAR database. These advances along with high-throughput screening are catalysing the discovery process of newer pharmacophores and modulators of K+ channels. This chapter aims to provide a basic understanding of K+ channels and offers an updated overview on the progress and opportunities of pharmacological approaches in the exploitation of these channels as therapeutic targets.

The identification of cannabinoid (CB) receptors has contributed to the state-of-the-art on the endocannabinoid system and its elements. Endocannabinoids (eCBs) are the endogenous agonists, derived from the conjugation of arachidonic acid with either ethanolamine (i.e. anandamide) or glycerol (i.e. 2-arachidonoylglycerol) acting as a lipid signaling mediator via two types of cannabinoid receptors (i.e. CB1 and CB2). Introduction of selective CB antagonists, inhibitors of eCB transport and metabolism, cannabinoid receptor-deficient mice and highlights on amidohydrolase have greatly facilitated the subsequent investigation of the eCB system. Moreover, modulation of the eCB system holds a promising therapeutic potential in the management of a myriad of pathophysiological conditions such as anxiety or mood disorders, neuropathic pain, multiple sclerosis, neurodegenerative diseases, osteoporosis, obesity and cancer among others. This chapter is comprehensively focused on the signal transduction and metabolic pathways, physiological roles, pharmacology and therapeutic potential of the endocannabinoids, with particular emphasis on cannabinoid addiction.