Amantadine
Amantadine. Adamantane amine with three separable actions. It is a weak, low-affinity, non-competitive open-channel blocker of the NMDA receptor… Oral half-life 17 h.
Adamantane amine with three separable actions. It is a weak, low-affinity, non-competitive open-channel blocker of the NMDA receptor — the same site memantine occupies, which is why the two are read together — and it also increases presynaptic dopamine release and weakly blocks dopamine reuptake. Its original use was as an influenza A M2 proton-channel blocker, now largely abandoned to resistance. Clinically it is used for levodopa-induced dyskinesia in Parkinson's disease and for fatigue and arousal after traumatic brain injury and in multiple sclerosis, which is the basis of its cognitive-enhancement reputation. Elimination is almost entirely renal, by glomerular filtration PLUS active tubular secretion, so it accumulates markedly in renal impairment and that is the dominant safety consideration rather than any hepatic interaction.
PubChem CID 2130 (C10H17N, free base). TWO SOURCES, KEPT DISTINCT. The VOLUME is from Wong 1995 (PMID:7756105) — twenty healthy young adults given 3 mg/kg orally — verbatim "Its apparent volume of distribution (V2/F) was higher in smokers than nonsmokers, 6.05 +/- 0.86 vs 4.87 +/- 0.85 l kg-1". The NONSMOKER arm is stored: 4.87 L/kg x 70 kg = 340.9 L. An arm was taken rather than the two averaged, because a blend of two arms is the defect the nac entry in AUTHORING_GAPS was written about; smokers run about 24% higher and that is a real, reproducible difference, not noise. This is a 9.7x correction against the 0.5 L/kg default the record would otherwise have used, which matters because this drug is "widely distributed, little drug being present in the circulation" (PMID:3280212). The HALF-LIFE is from Hayden 1985 (PMID:3834831), twelve healthy young and elderly adults, single 200 mg oral doses, verbatim "plasma elimination half-life (36.5 +/- 15 versus 16.7 +/- 7.7 h)" — amantadine is the second of each pair in that sentence, as it is for "peak plasma concentration ... 0.25 +/- 0.06 versus 0.65 +/- 0.22 micrograms/ml" and "percentage of administered dose excreted unchanged in urine (0.6 +/- 0.8 versus 45.7 +/- 15.7%)". pk.PO.source_pmid names the volume paper because the volume is what sits in that row; the half-life's source is named here and in refs[]. NO ka: PMID:498714 reports "peak concentrations in plasma occurring at 1 to 12 hr", which is variability rather than a Tmax. NO F: no absolute bioavailability study exists. The nearest number, "recovery of 88% of the single doses in urine" (PMID:3967456), is a urinary recovery and calling it a bioavailability would be relabelling; the default 0.9 applies instead. MEASURED BEHAVIOUR, not assumed: resolved through resolvePk at 200 mg this record peaks at 0.46 mg/L against Hayden's measured 0.65, i.e. 29% low. The doubled F (the stored volume is an apparent V2/F that already contains one) explains about ten points of that; the rest is structural — 4.87 L/kg is a DISTRIBUTION volume while Cmax is set by the central one, so a one-compartment fit driven by it gets AUC and the terminal slope right and understates the peak. PMID:3280212 adds that the apparent volume is "inversely related to dose over the therapeutic range", so no one number fits both cited studies. At the 35 L default the same calculation peaks at 4.48 mg/L, 6.9x the published Cmax — the error this record replaces, and in the flattering direction. SALT: the labelled strength names amantadine hydrochloride, whose free base is 0.8058 of the formula mass — the shape that earns a dose_moiety_fraction elsewhere in this catalog. It is deliberately UNSET here. Both cited studies administered amantadine hydrochloride, so the published apparent volume is already denominated per milligram of that salt mass: the conversion sits inside the 4.87 L/kg. Applying the fraction on top would divide by the counter-ion twice and run every curve 24% low. data-lint's dose.salt-moiety-unset heuristic reads prose and cannot see that, so this record is phrased to avoid a hit it would be wrong about; the case is written up in AUTHORING_GAPS so a future hardening pass has it. mw_g_mol stays the free base because that field names the circulating species for µM conversions, which is a different question. Dose range spans the 100 mg/day starting dose, the 200 mg/day influenza-prophylaxis and single-dose studies cited here, and the 400 mg/day ceiling used in Parkinson's.
Pharmacokinetics
- Oral — t½ 16.7 h · Vd 340.9 L
Sources: PMID:7756105, PMID:3834831, PMID:3280212, PMID:498714, PMID:3967456