Qualifies· moderateORCH-E030
Jurd/Zeller β3(N265M) line: propofol's immobility and hypnosis endpoints separate
- what the source states
- In the same β3(N265M) knock-in line used by Jurd et al. 2003, the endpoints of intravenous anesthesia dissociate: suppression of noxious-evoked movement (immobility) is abolished in the mutants, while loss-of-righting-reflex duration — the standard rodent surrogate for hypnosis — is profoundly reduced but not abolished.
- what we infer
- Sharpens what the receptor-level evidence in this case does and does not establish. The β3 mutation's cleanest, most complete effect is on immobility, a spinal endpoint; its effect on the consciousness-adjacent endpoint is real but partial. That distinction supports keeping the narrow claim (ORCH-C003) separate from the exhaustive one (ORCH-C004), and it means "change one amino acid and the drug stops working" is strictly true of immobility and only partly true of hypnosis.
- limitations
- Loss of righting reflex is a coarse surrogate for consciousness; a reduced-but-present hypnotic response does not establish where the residual effect acts.
- Bibliographic details incomplete (see source verificationNote); the finding is corroborated across independent descriptions but the exact journal/volume is unconfirmed.