Vincamine (20, 40, and 80 μM; 24 hours) protects human corneal epithelial cells (HCECs) from lipopolysaccharide (LPS) in a significant, concentration-dependent manner[1].
Vincamine (20, 40 and 80 μM; 24 hours) dramatically lowers the level of reactive oxygen species (ROS) in a dose-dependent manner in LPS-treated human corneal epithelial cells (HCECs)cells. Furthermore, following Vincamine administration, MDA levels are also markedly lowered while T-AOC and SOD levels rise in a dose-dependent manner[1].
Vincamine (20, 40 and 80 μM; 24 hours) dose-dependently restores TrxR activity in HCECs. Nevertheless, neither LPS nor Vincaminer can activate nor inhibit the intracellular activities of Trx, GR, or GPx[1].
Vincamine could activate GPR40 (EC50=6.28 µM) while DHA (a GPR40 ligand) served as a positive control (EC50=3.85 µM) in hGPR40-CHO cells[2].

Vincamine (intraperitoneal injection; 15 and 30 mg/kg/day; 6 weeks) improves glucose tolerance in type 2 diabetic model mice. It successfully reduces glycated hemoglobin and fasting blood glucose levels. In addition, it improves glucose-induced plasma insulin concentration and oral glucose tolerance without affecting basal insulin secretion in vivo[2].

Male and female db/db mice (BKS.Cg-Dock^7m+/+Lepr^db/J) and HFD/STZ-induced type 2 diabetic model mice
15 and 30 mg/kg/day
Intraperitoneal injection; 15 and 30 mg/kg/day; 6 weeks

Absorption, Distribution and Excretion
In a crossover study of six healthy volunteers the pharmacokinetics and the bioavailability of vincamine were studied after administration of two oral forms. All subjects received an oral dose of 60 mg vincamine. ...The drug generally follows a one-compartment kinetic model. The average value of Tmax is 1.4 +/- 0.5/hr with the tablets and 1 +/- 0.6/hr with the solution; the Cmax are, respectively, 155 +/- 82 micrograms . 1(-1) and 133 +/- 104 micrograms . 1(-1). The AUC are 443 +/- 156 micrograms . 1(-1) hr with the tablets and 315 +/- 178 micrograms . 1(-1) hr with the solution.
Vincamine HCl was biopharmaceutically and pharmacokinetically evaluated. For biopharmaceutical characterization of the drug the apparent lipoid/water partition coefficient (APC), pKa, extent of protein (bovine) binding and the erythrocyte (human) uptake were determined. Vincamine has an APC of 2.05, a pKa of 6.17, is 64% bound to plasma proteins, and is about 6% bound to erythrocytes. Because the gerbil was used as model in pharmacodynamic studies, the pharmacokinetic drug disposition was determined in this species and compared to parameters reported in the literature for other species. The terminal half-life is about 1 hour, the apparent volume of distribution 2.9 L/kg, and the total clearance is about 33.3 mL/min/kg. The parameters are comparable to other species including man. The brain concentration is about 5-fold that in plasma. A therapeutic steady state concentration for effectiveness in gerbils has been estimated to be 0.02 ug/mL.
Pharmacokinetic parameters of vincamine in rats were measured after oral administration of 20 mg base/kg bw and intravenous injection of 10 mg vincamine hydrochloride/kg bw. After oral administration, a bioavailability of 58% was found and the concentration/time curve showed a two-compartment open model. The following parameters were observed: an elimination half-life of 1.71 hours, a t-max of 1.27 hours, a C-max of 0.87 ug/ml, a total clearance of 0.818 1/h (higher than the plasma perfusion volume, which indicates a very quick metabolism in other organs in addition to the liver), and a volume of distribution of 2.018 liters. The amount of unchanged vincamine excreted was very low with 3 to 11% in urine and 2 to 5% in bile. Vincamine is taken up in high concentrations into the different organs resulting in the following ratios: lung/plasma 21, brain/plasma 14.6, kidneys/plasma 14.3, liver/plasma 8.9, heart/plasma 7.6. However, elimination from these organs was significantly more rapid than from plasma. After intravenous injection the pharmacokinetic parameters observed were an elimination half-life of 1.68 hours, a C-max of 5.46 ug/ml, a total clearance of 0.866 1/hour, and a volume of distribution of 2.104 liters. The values for elimination half-life, volume of distribution and total clearance did not differ significantly between oral and intravenous administration.
Pharmacokinetics of vincamine in dogs also followed a two-compartment open model. Doses of 10, 20 and 40 mg intravenously showed dose-dependent half-life and clearance rate. After oral administration of 20 mg vincamine hydrochloride, bioavailability ranged between 23 and 58%. Vincamine could be detected in the urine at up to 9.5% depending on urinary pH.
For more Absorption, Distribution and Excretion (Complete) data for VINCAMINE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
The metabolism of vincamine hydrochloride was studied in the rat after oral administration of the drug. Vincamine is almost completely metabolized, only a small fraction of the original compound being excreted in the urine. The metabolites detected in blood, urine and tissues were purified by preparative thin layer and column chromatography in several solvent systems, and analyzed by mass spectrometry. It was found that the main urinary metabolites were vincamine conjugates (sulphates and glucuronides). Two new metabolites were detected in all the biological fluids and specimens analyzed: these compounds are more polar than vincamine and their structure was characterized by mass spectrometry, I.R. and U.V. spectroscopy and confirmed by synthesis in our laboratory.[Vigano V et al; Farmaco
Vincamine is very extensively metabolised with only a small percentage of unchanged compound detectable in the urine. Radiolabel studies in rats after an oral dose of 10 mg/kg bw demonstrate the metabolic pathway of vincamine. On the one hand it is hydrolysed by the plasma esterases to the unstable vincaminic acid. The latter is quickly decarboxylised and oxidised to eburnamenine. On the other hand vincamine is hydroxylated to the major metabolite 6-beta-hydroxy-vincamine, which accounts for 40% of total urinary and biliary radioactivity, followed by 6-alpha-hydroxy-vtncamine (8%) and 6-keto-vincamine, the oxidized metabolite of both previous metabolites (about 10% of the administered dose). 6-Keto-vincamine is eliminated by conjugation. The same metabolites (hydroxy.-keto) could also be detected in the urine of rabbits, dogs and man. Within 72 hours 40% of the total radioactivity are excreted in twine and 23% in the feces.

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Biological Half-Life
After intravenous injection /of vincamine hydrochloride to rats/ the pharmacokinetic parameters observed were an elimination half-life of 1.68 hours /Vincamine hydrochloride/.
The following parameters were observed /after oral administration of 20 mg/kg vincamine (base) to rats/: an elimination half-life of 1.71 hours...
After oral administration of 4 mg vincamine hydrochloride/kg bw /in dogs/ an elimination half-life of 4.5 hours (longer than for rats) and a total clearance of 0.52 1/hour were observed. /vincamine hydrochloride/
Half-life of elimination for the solution was 0.57 to 1.07 hours/for 169 mg vincamine hydrochloride and 33.81 mg vincamine hydrochloride control-released tablets respectively/.
Vincamine HCl was biopharmaceutically and pharmacokinetically evaluated. ...The terminal half-life is about 1 hour... .

[1]. Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice. J Endocrinol. 2019 Feb 1;240(2):195-214.

[2]. Vincamine prevents lipopolysaccharide induced inflammation and oxidative stress via thioredoxin reductase activation in human corneal epithelial cells. Am J Transl Res . 2018 Jul 15;10(7):2195-2204. eCollection 2018.

Vincamine is a vinca alkaloid, an alkaloid ester, an organic heteropentacyclic compound, a methyl ester and a hemiaminal. It has a role as an antihypertensive agent, a vasodilator agent and a metabolite. It is functionally related to an eburnamenine.
Vincamine is a monoterpenoid indole alkaloid obtained from the leaves of *Vinca minor* with a vasodilatory property. Studies indicate that vincamine increases the regional cerebral blood flow.
Vincamine has been reported in Vinca difformis, Vinca major, and other organisms with data available.
A major alkaloid of Vinca minor L., Apocynaceae. It has been used therapeutically as a vasodilator and antihypertensive agent, particularly in cerebrovascular disorders.

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Mechanism of Action
... At concentrations of 1, 10 and 100 microM, a five-minute perfusion with vincamine did not affect the synaptically-mediated activation of pyramidal neurons evoked by stimulation of the Schaffer-commissural fiber system. The effect of vincamine on the excitability of the pyramidal neurons was investigated by studying its effect on the antidromically-elicited field potential and the input-output relation of Schaffer-commissural fiber input. No effect on either of the two parameters was seen at a concentration of 100 microM of vincamine. Vincamine ... attenuate both the post-tetanic (PTP) and long-term potentiation (LTP) evoked by repetitive stimulation of the Schaffer-commissural fiber system. At a concentration of 100 microM of vincamine, PTP was significantly reduced and LTP was almost completely suppressed.
Vincamine's function and therapeutic use as a vasodilating agent, especially at the level of the central nervous system, has been proven after an intravenous administration of 30 mg over a period of 20 minutes in Mongolian gerbils by an increase of cerebral blood flow of approximately 10% and of regional cerebral blood flow in areas with insufficient blood supply by approximately 15%. The mechanism of this vascular action, while not fully clear, seems to be partly due to a reserpine-like noradrenaline depleting effect. Hence, its sedative effects are similar to reserpine

C21H26N2O3

354.4427

354.194

C, 71.16; H, 7.39; N, 7.90; O, 13.54

1617-90-9

42971-09-5 (Vinpocetine); 4880-92-6 (Apovincamine); 4429-63-4 (Tabersonine); 4880-88-0 (CH846; CH-846; CH 846; Vinburnine; Eburnal; Eburnamonine); 19877-89-5 (Vincanol; Vincanolum); 68779-67-9 (Vindeburnol)

15376

Yellow crystals from acetone or methanol

1.4±0.1 g/cm3

508.9±50.0 °C at 760 mmHg

232ºC (dec.)

261.6±30.1 °C

0.0±1.4 mmHg at 25°C

1.682

3.1

1

4

3

26

598

3

O([H])[C@]1(C(=O)OC([H])([H])[H])C([H])([H])[C@]2(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])N3C([H])([H])C([H])([H])C4C5=C([H])C([H])=C([H])C([H])=C5N1C=4[C@@]32[H]

RXPRRQLKFXBCSJ-GIVPXCGWSA-N

InChI=1S/C21H26N2O3/c1-3-20-10-6-11-22-12-9-15-14-7-4-5-8-16(14)23(17(15)18(20)22)21(25,13-20)19(24)26-2/h4-5,7-8,18,25H,3,6,9-13H2,1-2H3/t18-,20+,21+/m1/s1

methyl (15S,17S,19S)-15-ethyl-17-hydroxy-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18)-tetraene-17-carboxylate

Vincamine; Vinca Minor extract; periwinkle extract; Angiopac; Devincan; Equipur; Minorin; Novicet; Oxybral; Perval; Sostenil; Tripervan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 3~25 mg/mL (8.5~70.5 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)