LSD

The input

First-order gastrointestinal absorption with a rate constant giving a peak near one hour, and a bioavailability reduced by first-pass metabolism. Both are class placeholders; where a compound has a published oral F it overrides this. Bioavailability for this route is 0.3 and the absorption rate constant 1.2 h⁻¹, both properties of the route rather than of LSD.

One compartment with first-order absorption. It cannot show a distribution phase, so the first minutes after an intravenous dose are the least trustworthy part of the curve. Peak effect-site concentration is 0.55 nM.

O = C/(C+Kᵢ) at the effect-site concentration above. The Kᵢ is measured and this archive holds it; the C is modelled. Equilibrium is assumed at every instant, with no receptor reserve, no active metabolite and no tolerance.

• 5-HT218%
• 5-HT1A *64%
• 5-HT7 * †58%
• 5-HT2A * †53%
• 5-HT2B *36%
• 5-HT2C *33%
• 5-HT6 *30%
• 5-HT5B *14%
• 5-HT1B *12%
• 5-HT1D *8%
• 5-HT5A *6%
• Alpha2A *4%
• D2 *3%
• D3 *2%

† The archive holds measurements of this pair that disagree by more than a hundredfold, so the single number beside it is not settled. The strongest is shown — in this archive the strongest measurement is usually the best one rather than an outlier, because weak values are disproportionately old tissue preparations — but the range is what the sources actually support: 5-HT7 0.40–200 nM across 15; 5-HT2A 0.47–5,300 nM across 40.

* This archive holds no pChEMBL value for the pair, and holds one for others of this compound — so the absence is ChEMBL’s, not a gap in the harvest. ChEMBL withholds a pChEMBL where the activity is not a comparable, meaningful result: an inexact relation, an unrecognised type, or a screen the depositor marked inactive. The concentration is shown because it is what the archive holds, and it is ranked below everything vouched for because it is not evidence of binding. Ketamine against the APE1 endonuclease is the example that earned this footnote: ChEMBL records that screen as inactive, and read as an affinity it made a DNA-repair enzyme ketamine’s tightest binder by two orders of magnitude.

Modelled regional engagement

Occupancy at each target multiplied by that target’s transcript level in the region, summed. This product is the model speaking. A dossier’s Systems plate deliberately refuses to compute it, because there it would read as a finding; here it is an output with its assumptions on the page. Transcript is not receptor density, and a region shaded here is a region where the model says binding could occur, not one shown to be affected.

And nothing checks it. The concentration plot above carries reported milestones because human studies state times; this figure has no counterpart. The human imaging work this archive cites reports connectivity change across a cortical parcellation, which is a different quantity in a different set of regions — the atlas holds the cortex as one — so it can neither confirm nor contradict the shading here, and translating it onto these thirteen regions would assert a correspondence nobody has published.

Shading is on a fixed scale — the strongest engagement reached anywhere during the whole run — so the figures dim as the compound clears instead of renormalising to whatever the current instant happens to hold. Outlines from the EMBL-EBI Anatomogram, the same plates the dossiers use.

Parameters

The whole model is these five numbers plus the route. Each says whether anyone measured it for LSD. Edit any of them; nothing here is written back to the archive.