Abstract
Objective: Vinpocetine has been shown to enhance memory in animal models, with possible cognitive benefit in humans. The present study sought to demonstrate if vinpocetine can enhance cognition in healthy volunteers or patients with epilepsy. In addition, we compare blood levels of vinpocetine and its active metabolite (apovincaminic acid; AVA) in humans and animals to further characterize factors related to possible therapeutic benefit. Methods: The cognitive effects of vinpocetine were assessed in healthy adult volunteers (n = 8) using a double-blind, randomized, crossover design at single doses (placebo, 10, 20, and 60 mg oral). Cognitive effects of vinpocetine in patients with focal epilepsy (n = 8) were tested using a double-blind, randomized, crossover design at single doses (placebo, 20 mg oral) followed by one-month open label at 20 mg oral three times a day. The neuropsychological battery included both computerized and non-computerized tests. Levels of vinpocetine and AVA in the human studies were compared to levels in 45 mice across time dosed at 5–20 mg/kg intraperitoneal of vinpocetine. Results: No significant cognitive benefits were seen in healthy volunteers or patients with epilepsy. No appreciable side effects occurred. Vinpocetine and AVA levels were lower in humans than animals. Conclusions: Vinpocetine was well tolerated, but was not associated with positive cognitive effects. However, blood levels obtained in humans were substantially less than levels in animals obtained from dosages known to be effective in one model. This suggests that higher dosages are needed in humans to assess vinpocetine's cognitive efficacy.
| Original language | English (US) |
|---|---|
| Article number | 107988 |
| Journal | Epilepsy and Behavior |
| Volume | 119 |
| DOIs | |
| State | Published - Jun 1 2021 |
Bibliographical note
Funding Information:This study was sponsored in part by James and Jen Jacoby, and by Stanford University . The sponsors were not involved in study design, data collection, analyses, or writing of the report.
Funding Information:
The authors thank James and Jen Jacoby for their support. Dr. Meador designed, conceptualized and oversaw study; obtained funding, analyzed the data; drafted the manuscript, and approved final submission. All authors reviewed, offered comments and approved the manuscript. In addition, Dr. Leeman-Markowski helped design the study, wrote the first draft of the IND, and assessed subjects; Dr. Illamola set up the blood assays and ran the levels; Dr. Medina dosed and provided the blood samples from animals; Mr. Seliger established processes, completed paperwork with institution and FDA, tested subjects and helped with analyses; Ms. Novak, Ms. Lin, and Dr. Ivanisevic tested subjects and collected data; Dr. Razavi assessed subjects; Dr. Marino oversaw the blood assays; Mr. Boyd set up computerized testing and provided processed data from tests; and Dr. Loring helped design study and conducted the statistical analyses. Dr. Meador has received research support from the National Institutes of Health and Sunovion Pharmaceuticals, and travel support from UCB Pharma. The Epilepsy Study Consortium pays Dr. Meador's university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, and UCB Pharma. Dr. Leeman-Markowski reports nothing to disclose; Dr. Medina reports nothing to disclose; Dr. Illamola reports nothing to disclose; Mr. Seliger reports nothing to disclose; Ms. Novak reports reports nothing to disclose; Ms. Lin reports nothing to disclose; Dr. Ivanisevic reports nothing to disclose; Dr. Razavi reports research support from NeuoPace and holds stock ownership in CortexXus; Dr. Marino reports nothing to disclose; Mr. Boyd is the CEO of CNS Vital Signs; and Dr. Loring reports support for research from NIMH and NINDS, consultant from NeuroPace, editorial stipends from Epilepsia and Neuropsychology Review, and book royalties from Oxford University Press. This study was sponsored in part by James and Jen Jacoby, and by Stanford University. The sponsors were not involved in study design, data collection, analyses, or writing of the report.
Funding Information:
Dr. Meador has received research support from the National Institutes of Health and Sunovion Pharmaceuticals, and travel support from UCB Pharma. The Epilepsy Study Consortium pays Dr. Meador’s university for his research consultant time related to Eisai, GW Pharmaceuticals, NeuroPace, Novartis, Supernus, Upsher-Smith Laboratories, and UCB Pharma. Dr. Leeman-Markowski reports nothing to disclose; Dr. Medina reports nothing to disclose; Dr. Illamola reports nothing to disclose; Mr. Seliger reports nothing to disclose; Ms. Novak reports reports nothing to disclose; Ms. Lin reports nothing to disclose; Dr. Ivanisevic reports nothing to disclose; Dr. Razavi reports research support from NeuoPace and holds stock ownership in CortexXus; Dr. Marino reports nothing to disclose; Mr. Boyd is the CEO of CNS Vital Signs; and Dr. Loring reports support for research from NIMH and NINDS, consultant from NeuroPace, editorial stipends from Epilepsia and Neuropsychology Review, and book royalties from Oxford University Press.
Publisher Copyright:
© 2021 Elsevier Inc.
Keywords
- Antiseizure medication
- Cognition
- Epilepsy
- Memory
- Vinpocetine