non-competitive inhibition
In non-competitive inhibition, the inhibitor does not fight the substrate for its seat — it sits somewhere else entirely and still spoils the show. By binding a separate site, it changes the target's shape or behaviour so the target works less well even when substrate is fully bound.
Because the two molecules occupy different sites, adding more substrate cannot displace the inhibitor: the block is insurmountable. The signature is a fall in maximal rate (Vmax) or maximal response that no amount of substrate can rescue — in the classic case Km is unchanged while Vmax drops, effectively removing a fraction of functional target.
This often works through an allosteric site, and underlies many useful modulators and insurmountable receptor antagonists. Compared with competitive inhibition, the effect is more robust to surges in the body's own substrate or signal, but it caps the maximal achievable response, which can be either a therapeutic asset or a liability depending on the goal.
Ketamine is a non-competitive NMDA-receptor antagonist: it binds within the ion channel rather than at the glutamate site, blocking it in a way that more glutamate cannot reverse.
A non-competitive inhibitor binds a distinct site and cannot be out-competed by substrate.
Strictly, 'non-competitive' means Km is unchanged and Vmax falls. The broader, looser usage covers any inhibitor binding away from the active site that substrate cannot out-compete.