When a receptor is stimulated continuously, the cell defends itself. Within minutes, the receptor is phosphorylated and uncoupled from its signal (desensitisation); within hours it can be removed from the cell surface (internalisation); and with prolonged exposure the cell can make fewer receptors (downregulation).
Speed is what separates tachyphylaxis from classic tolerance: the first appears within a few exposures; the second over days or weeks. In both cases, the same amount produces less and less effect.
Hormonal axes that work in pulses are especially sensitive. A classic example: GnRH given in pulses stimulates the pituitary, but given continuously it desensitises it and ends up suppressing the axis. That is why in many studies with secretagogues or kisspeptin the exposure pattern matters as much as the amount.
Tachyphylaxis explains why some studies include exposure-free periods or compare pulsatile and continuous schedules. Ignoring it leads to labelling as “ineffective” a compound that was simply studied with the wrong pattern.
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Definition for educational and scientific purposes. It is not medical advice or a recommendation for use. NeoPeptidos products are sold labelled for research use only (RUO).