In vitro characterization of transport and metabolism of the alkaloids: vincamine, vinpocetine and eburnamonine

Abstract

The developed simple, sensitive and reliable UPLC analysis methods can be utilized in future in vitro and in vivo studies. The three alkaloids demonstrated minimal interaction with the drug efflux transporters Pgp and Bcrp, concordant with the ability of these alkaloids to cross the BBB. The relative metabolic stability of eburnamonine compared to the other alkaloids suggests the use of eburnamonine or its derivatives as lead compounds for the development of antitumor and nootropic agents that need to cross the BBB and produce their pharmacological effects in the CNS.

Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice

“…Vincamine (Fig. 1A) is a monoterpenoid indole alkaloid found in the Madagascar periwinkle (Fandy et al 2016). It increases cerebral blood flow, oxygen consumption and glucose utilization and improves dementia and memory disturbance (Hagstadius et al 1984).…”

“…It increases cerebral blood flow, oxygen consumption and glucose utilization and improves dementia and memory disturbance (Hagstadius et al 1984). Vincamine is commercially available in the United States as a health care product with nootropic function (Fandy et al 2016). Recently, common features between β-cells and neurons have been widely investigated.…”

The Effect of Vinpocetine on Human Cytochrome P450 Isoenzymes by Using a Cocktail Method

“…Vinpocetine readily enters the bloodstream from the stomach and gastrointestinal tract and consequently passes the blood-brain barrier. Vinpocetine was metabolized exclusively in the liver of dogs and humans, whereas in rats extrahepatic metabolism seems to be important [ 8 , 9 ]; apovincaminic acid is the main hydrolysis metabolite of vinpocetine and is eliminated from the body through the kidneys [ 10 ].…”

“…Although there have been some investigations of DDI of vinpocetine [ 9 , 16 , 17 ], information on the CYP enzyme-mediated drug metabolism has not been previously studied. Owing to the fact that the use of in vitro data to predict the inhibition potential of a drug is wonderful with simple, convenient, and high throughput [ 18 ], the major objective of the present study was to investigate the effects of vinpocetine on the CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 enzymes, which are primarily involved in drug metabolism, and then to predict any DDIs when vinpocetine is coadministered with other drugs metabolized by CYPs.…”

15‐Methylene‐Eburnamonine Kills Leukemic Stem Cells and Reduces Engraftment in a Humanized Bone Marrow Xenograft Mouse Model of Leukemia

“…17 The alkaloids, (−)-eburnamonine ( 1 ) and vincamine ( 2 ), are also isolated from the Madagascar periwinkle (Figure 1), 18 and display a favorable pharmacokinetic profile. 19 Recently, we designed and synthesized (−)-15-methylene-eburnamonine ( 3 ) to impart antiproliferative activity through structural modification. 20 Specifically, the analogue 3 displays a critical enone group, 21 and this functional group imparts cytotoxic properties similar to other enone-bearing natural products, such as parthenolide ( 4 ) 22 and andrographolide ( 5 ).…”