| Description: |
Galanthaminone (Narwedin) is a competitive and reversible cholinesterase (AChE) inhibitor; is used for the treatment of mild to moderate Alzheimer's disease and various other memory impairments. |
| Targets: |
AChR | IL Receptor |
| In vitro: |
| European Journal of Drug Metabolism and Pharmacokinetics,1987,12(1):25-30. | | In vitro metabolism of galanthamine hydrobromide (Nivalin®) by rat and rabbit liver homogenate[Reference: WebLink] | The metabolism of galanthamine hydrobromide (Nivalin®) was investigated in rat and rabbit liver homogenates.
METHODS AND RESULTS:
Experiments were carried out varying several parameters of incubation: substrate (galanthamine hydrobromide, galanthamine, Galanthaminone and epigalanthamine), cofactor enrichment (NADPH, NADP/G-6-P, NAD), pH (7.4 and 9.3), time of incubation. Substrates and metabolites were identified and quantitatively determined by GC/MS. In vitro metabolism in rat liver homogenate was negligible. The experiments with rabbit liver homogenate indicated, that galanthamine was actively metabolised the major metabolites being the oxidised product — Galanthaminone, and the isomer of galanthamine — epigalantamine.
CONCLUSIONS:
The experimental results show that the metabolism of galanthamine is substrate and product stereoselective. |
|
| In vivo: |
| Clin Pharmacol Ther. 1991 Oct;50(4):420-8. | | Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition.[Pubmed: 1914378] |
METHODS AND RESULTS:
Measurements were done to determine the plasma concentrations of galanthamine and two of its metabolites, as well as the corresponding inhibition of acetylcholinesterase activity in erythrocytes after applying 5 and 10 mg galanthamine hydrobromide as a constant-rate intravenous infusion for 30 minutes and single oral doses of 10 mg in eight healthy male volunteers.
The data obtained revealed first-order pharmacokinetics, complete oral bioavailability, and a mean terminal half-life of 5.68 hours (95% confidence interval, 5.17 to 6.25 hours). Renal clearance accounted for only 25% of the total plasma clearance (CL = 0.34 L.kg-1.hr-1). Only negligible quantities of the putative metabolites, epigalanthamine and Galanthaminone, were detected in blood and urine. The inhibition of acetylcholinesterase activity was closely correlated with the pharmacokinetics of galanthamine, a median maximal value of 53% being achieved by applying 10 mg galanthamine intravenously.
CONCLUSIONS:
Analysis of in vitro and ex vivo concentration responses revealed no differences, indicating that no metabolites of galanthamine exert additional inhibition of acetylcholinesterase activity. |
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