Reverse Pharmacology

Introduction & definition

• Definition — reverse pharmacology (RP) is the integrating science of developing candidate drugs from a clinical lead to experiential hits and leads by transdisciplinary exploratory studies, and ultimately to understanding their mechanism of action — then confirming the candidate from experimental back to clinical use on the basis of safety, efficacy and acceptability.
• Core idea — in its India/Ayurveda framing RP is essentially a rediscovery of a drug's activity and its mechanism of action — the molecule is already in human use, and the science works backwards to validate and explain it.
• Directional contrast — conventional ("forward") pharmacology runs laboratory → clinic (target → molecule → animal → human); reverse pharmacology runs clinic / bedside observation → laboratory (observed human effect → mechanism → formal validation).
• Inverted evidence order — RP starts from a documented clinical observation / experience and then seeks the experimental and mechanistic basis, rather than starting from a molecular target and seeking a clinical effect.
• Two senses of the term — the literature uses "reverse pharmacology" in two related ways — both share "work backwards from an observed entity to its mechanism": (1) the India / Ayurveda sense (clinic-to-lab rediscovery of traditional-medicine leads), and (2) the molecular / orphan-receptor sense (deorphanising a receptor by finding its endogenous ligand and working back to physiology).
• Where it sits — presented in Medhi Ch.39 as a "recent advance," RP is distinct from — but related to — translational medicine and microdosing / Phase 0; the three are complementary strategies for accelerating drug development, not synonyms.