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First in human study with a prodrug of galantamine: Improved benefit-risk ratio?
INTRODUCTION: Gln-1062 (Memogain) is a pharmacologically inactive prodrug of galantamine. Owing to its lipophilic nature, it preferentially enters the brain, where it is cleaved into active galantamine. Gln-1062 is expected to have fewer peripheral side effects than other cholinesterase inhibitors,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644278/ https://www.ncbi.nlm.nih.gov/pubmed/29067291 http://dx.doi.org/10.1016/j.trci.2015.12.003 |
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author | Baakman, Anne C. 't Hart, Ellen Kay, Denis G. Stevens, Jasper Klaassen, Erica S. Maelicke, Alfred Groeneveld, Geert J. |
author_facet | Baakman, Anne C. 't Hart, Ellen Kay, Denis G. Stevens, Jasper Klaassen, Erica S. Maelicke, Alfred Groeneveld, Geert J. |
author_sort | Baakman, Anne C. |
collection | PubMed |
description | INTRODUCTION: Gln-1062 (Memogain) is a pharmacologically inactive prodrug of galantamine. Owing to its lipophilic nature, it preferentially enters the brain, where it is cleaved into active galantamine. Gln-1062 is expected to have fewer peripheral side effects than other cholinesterase inhibitors, with improved effectiveness. METHODS: This was a double-blind, comparator and placebo-controlled, sequential cohort, single ascending dose study in 58 healthy subjects with Gln-1062 in doses of 5.5, 11, 22, 33, and 44 mg, compared with oral galantamine 16 mg and donepezil 10 mg. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed. RESULTS: Gln-1062 doses up to 33 mg were well tolerated and induced a dose-dependent increase in the plasma concentrations of Gln-1062 and galantamine. Gln-1062 had a dose-dependent positive effect on verbal memory and attention, mainly in the first hours after drug administration. DISCUSSION: Gln-1062 was better tolerated than galantamine in doses with the same molarity and led to improved effects in cognitive tests. This is most likely caused by the more favorable distribution ratio between peripheral and central cholinesterase inhibition. These results give reason for further exploration of this compound. |
format | Online Article Text |
id | pubmed-5644278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56442782017-10-24 First in human study with a prodrug of galantamine: Improved benefit-risk ratio? Baakman, Anne C. 't Hart, Ellen Kay, Denis G. Stevens, Jasper Klaassen, Erica S. Maelicke, Alfred Groeneveld, Geert J. Alzheimers Dement (N Y) Featured Article INTRODUCTION: Gln-1062 (Memogain) is a pharmacologically inactive prodrug of galantamine. Owing to its lipophilic nature, it preferentially enters the brain, where it is cleaved into active galantamine. Gln-1062 is expected to have fewer peripheral side effects than other cholinesterase inhibitors, with improved effectiveness. METHODS: This was a double-blind, comparator and placebo-controlled, sequential cohort, single ascending dose study in 58 healthy subjects with Gln-1062 in doses of 5.5, 11, 22, 33, and 44 mg, compared with oral galantamine 16 mg and donepezil 10 mg. Safety, tolerability, pharmacokinetics, and pharmacodynamics were assessed. RESULTS: Gln-1062 doses up to 33 mg were well tolerated and induced a dose-dependent increase in the plasma concentrations of Gln-1062 and galantamine. Gln-1062 had a dose-dependent positive effect on verbal memory and attention, mainly in the first hours after drug administration. DISCUSSION: Gln-1062 was better tolerated than galantamine in doses with the same molarity and led to improved effects in cognitive tests. This is most likely caused by the more favorable distribution ratio between peripheral and central cholinesterase inhibition. These results give reason for further exploration of this compound. Elsevier 2016-01-20 /pmc/articles/PMC5644278/ /pubmed/29067291 http://dx.doi.org/10.1016/j.trci.2015.12.003 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Featured Article Baakman, Anne C. 't Hart, Ellen Kay, Denis G. Stevens, Jasper Klaassen, Erica S. Maelicke, Alfred Groeneveld, Geert J. First in human study with a prodrug of galantamine: Improved benefit-risk ratio? |
title | First in human study with a prodrug of galantamine: Improved benefit-risk ratio? |
title_full | First in human study with a prodrug of galantamine: Improved benefit-risk ratio? |
title_fullStr | First in human study with a prodrug of galantamine: Improved benefit-risk ratio? |
title_full_unstemmed | First in human study with a prodrug of galantamine: Improved benefit-risk ratio? |
title_short | First in human study with a prodrug of galantamine: Improved benefit-risk ratio? |
title_sort | first in human study with a prodrug of galantamine: improved benefit-risk ratio? |
topic | Featured Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644278/ https://www.ncbi.nlm.nih.gov/pubmed/29067291 http://dx.doi.org/10.1016/j.trci.2015.12.003 |
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