Tachyphylaxis
A rapid decrease in the response to a drug after repeated doses over a short period. Tachyphylaxis can limit the effectiveness of certain peptide compounds and is an important consideration in dosing regimen design. The phenomenon is distinct from the slower development of tolerance.
Technical Context
Tachyphylaxis occurs rapidly (minutes to hours) upon repeated or continuous exposure, distinguishing it from the slower development of tolerance (days to weeks). Mechanisms include receptor phosphorylation, beta-arrestin recruitment (which uncouples the receptor from G-protein signalling), and depletion of downstream signalling intermediates. In peptide therapeutics, the GnRH agonist mechanism exploits tachyphylaxis — continuous GnRH receptor stimulation leads to rapid desensitisation and subsequent downregulation. For some peptide drugs, tachyphylaxis to side effects (like nausea with GLP-1 RAs) is beneficial, while tachyphylaxis to therapeutic effects would be problematic. Understanding tachyphylaxis potential guides dosing interval design.