PHARMACOLOGY OF RECEPTORS AND MOLECULAR MECHANISMS OF DRUG SEARCHING: INTEGRATED CLINICAL PHARMACOLOGY, PHARMACODYNAMIC, PHARMACOKINETIC, PHARMACOTHERAPEUTIC, PHARMACOGENOMIC, THERAPEUTIC DRUG MONITORING, EVIDENCE-BASED, AND PRECISION MEDICINE APPROACHES
DOI:
https://doi.org/10.52340/spectri.2026.13.01.05Keywords:
Receptor pharmacology, drug discovery, G protein–coupled receptors, signal transduction, agonist, integrated pharmacologyAbstract
Receptors are dynamic macromolecules that transduce chemical signals into biological responses and serve as the principal targets of modern therapeutics. This review surveys current concepts in receptor pharmacology and their application to drug discovery and development. Receptor-mediated signal transduction is examined across the major receptor families, including G protein–coupled receptors, ligand-gated and voltage-gated ion channels, nuclear receptors, and receptor tyrosine kinases, with emphasis on the second messengers, kinase cascades, and transcriptional programs that they engage. Classical receptor theory is reviewed alongside modern extensions that incorporate receptor efficacy, constitutive activity, receptor reserve, allosteric modulation, and biased agonism. Intracellular signal propagation is discussed as a network-level phenomenon shaped by cross-talk, feedback regulation, scaffold proteins, and compartmentalised signalling, providing the conceptual basis for network pharmacology. Drug-discovery strategies are then considered, from target identification and validation, high-throughput and phenotypic screening, and structure-based and fragment-based design to computational approaches, medicinal-chemistry optimisation, and the management of resistance, tolerance, and translational risk. Emerging modalities — allosteric modulators, agonists, targeted protein degraders (PROTACs), molecular glues, and covalent inhibitors — are discussed alongside the integration of receptor pharmacology with systems biology, biomarker-guided therapy, and personalised medicine. The review concludes that progress in receptor pharmacology will depend on controlling receptor conformational states, pathway selectivity, and tissue context rather than on maximising target affinity alone.
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