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Inverse agonism at serotonin and cannabinoid receptors

Contemporary receptor theory was developed to account for the existence of constitutive activity, as defined by the presence of receptor signaling in the absence of any ligand. In vitro studies with a variety of cell types have revealed the existence of constitutive activity and inverse agonism at a large number of receptors and also additional complexities of ligandreceptor interactions. Thus, ligands acting at a constitutively active receptor can act as agonists, antagonists, and/or inverse agonists, and these pharmacological characteristics can differ for an individual ligand depending upon the receptor response measured and the physiological state of the system under study. Studies with a variety of cell types have established that the serotonin 5-HT 2A and 5-HT2C receptors and the cannabinoid CB1 receptor demonstrate constitutive activity and inverse agonism in vitro. Serotonin and cannabinoid receptors are involved in a large number of physiological and behavioral functions. The possible existence of constitutive activity and inverse agonism at these receptors in vivo would provide new avenues for drug development. Recent studies have provided compelling evidence that both the serotonin 5-HT2A and 5-HT2C receptors and cannabinoid CB1 receptor demonstrate inverse agonism and constitutive activity also in vivo. This chapter describes our current knowledge of constitutive activity in vitro and then examines the evidence for constitutive activity in vivo.

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Reference£º
Piperidine – Wikipedia,
Piperidine | C5H23986N – PubChem