Colchicine

Category: alkaloid

Aliases: Colcrys, Mitigare

Pharmacological Mechanism

Binds β-tubulin at the vinca-site → blocks microtubule polymerisation → inhibits neutrophil chemotaxis, NLRP3 inflammasome assembly, and intracellular trafficking. Low-dose indication in stable CAD (LoDoCo2 trial 2020) — reduces recurrent MI via inflammasome suppression. Narrow therapeutic index — CYP3A4 and P-gp inhibitors drastically raise exposure and toxicity.

Half-Life (t½)

PO: 31h

Dosing Guidelines

PO: Typical 1.2 mg (Range: 1.2–1.2 mg)

Target Organ Systems

cardiovascular
digestive
immune-hematologic

Interactions

Cyclosporine (contraindicated): P-gp + CYP3A4 inhibition → fatal colchicine toxicity reported. Avoid or dose-reduce ≥75%. [Giacomini 2010]
Statins (caution): Additive myopathy / rhabdomyolysis risk. [Graham 2004]
Piperine (caution): P-gp + CYP3A4 inhibition raises colchicine exposure toward toxic range. [Giacomini 2010]

Pathways It Modulates

Atherosclerosis plaque pathology (inhibitor) — NLRP3 + microtubule → ↓plaque inflammation
cGAS-STING cytosolic DNA sensing → type I IFN (inhibitor) — microtubule → ↓STING trafficking
Neuroinflammation (inhibitor) — NLRP3 + microtubule trafficking
NLRP3 inflammasome (inhibitor) — NLRP3 inflammasome assembly + microtubule effects on neutrophil migration
Pyroptosis (inhibitor) — NLRP3 → pyroptosis (microtubule disruption)
TLR (Toll-like receptor) innate signaling (inhibitor) — TLR2/4 + microtubule → ↓inflammasome

Chemical Identifiers

PubChem CID: 6167
Formula: C22H25NO6
Molecular weight: 399.44 g/mol
InChIKey: IAKHMKGGTNLKSZ-INIZCTEOSA-N
SMILES: CC(=O)N[C@H]1CCC2=CC(=C(C(=C2C3=CC=C(C(=O)C=C13)OC)OC)OC)OC