Pharmacological aspects of (-)-Deprenyl

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10-9-10-13 M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency.

Original languageEnglish
Pages (from-to)2017-2031
Number of pages15
JournalCurrent Medicinal Chemistry
Volume11
Issue number15
Publication statusPublished - Aug 2004

Fingerprint

Selegiline
Pharmacology
Monoamine Oxidase
Metabolites
Neurodegenerative diseases
Metabolism
Neurodegenerative Diseases
Dopamine
Dopamine Agents
Mitochondria
Pharmacokinetics
Neurotoxins
Cell culture
Cholinergic Agents
Antidepressive Agents
Parkinson Disease
Reactive Oxygen Species
Brain
Appointments and Schedules
Cell Death

Keywords

  • Antiapoptotic activity
  • Dopamine potentiation
  • MAO-B
  • Neurodegenerative diseases
  • R-(-)-deprenyl
  • Selegiline

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Pharmacological aspects of (-)-Deprenyl. / Magyar, K.; Pálfi, M.; Tábi, T.; Kalász, H.; Szende, B.; Szökő, É.

In: Current Medicinal Chemistry, Vol. 11, No. 15, 08.2004, p. 2017-2031.

Research output: Contribution to journalArticle

@article{92bdc71eedc84f3bbac0d0bb0f76063b,
title = "Pharmacological aspects of (-)-Deprenyl",
abstract = "Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10-9-10-13 M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency.",
keywords = "Antiapoptotic activity, Dopamine potentiation, MAO-B, Neurodegenerative diseases, R-(-)-deprenyl, Selegiline",
author = "K. Magyar and M. P{\'a}lfi and T. T{\'a}bi and H. Kal{\'a}sz and B. Szende and {\'E}. Sz{\"o}kő",
year = "2004",
month = "8",
language = "English",
volume = "11",
pages = "2017--2031",
journal = "Current Medicinal Chemistry",
issn = "0929-8673",
publisher = "Bentham Science Publishers B.V.",
number = "15",

}

TY - JOUR

T1 - Pharmacological aspects of (-)-Deprenyl

AU - Magyar, K.

AU - Pálfi, M.

AU - Tábi, T.

AU - Kalász, H.

AU - Szende, B.

AU - Szökő, É.

PY - 2004/8

Y1 - 2004/8

N2 - Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10-9-10-13 M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency.

AB - Deprenyl, the selective irreversible inhibitor of monoamine oxidase-B (MAO-B), has been synthesised as a potential antidepressant, however, due to its dopamine potentiating capacity, became a registered drug in the treatment of Parkinson's disease. Deprenyl possesses a wide range of pharmacological activities; some of them are not related to its MAO-B inhibitory potency. Beside its dopamine potentiating effect, it renders protection against a number of dopaminergic, cholinergic and noradrenergic neurotoxins with a complex mechanism of action. By inducing antioxidant enzymes and decreasing the formation of reactive oxygen species, deprenyl is able to combat an oxidative challenge implicated as a common causative factor in neurodegenerative diseases. In a dose substantially lower than required for MAO-B inhibition (10-9-10-13 M), deprenyl interferes with early apoptotic signalling events induced by various kinds of insults in cell cultures of neuroectodermal origin, thus protecting cells from apoptotic death. Deprenyl requires metabolic conversion to a hitherto unidentified metabolite to exert its antiapoptotic effect, which serves to protect the integrity of the mitochondrion by inducing transcriptional and translational changes. Pharmacokinetic and metabolism studies have revealed that deprenyl undergoes intensive first pass metabolism, and its major metabolites also possess pharmacological activities. The ratio of the parent compound and its metabolites reaching the systemic circulation and the brain are highly dependent on the routes of administration. Therefore, in the treatment of neurodegenerative diseases, reconsideration of the dosing schedule, by lowering the dose of deprenyl and choosing the most appropriate route of administration, would diminish undesired adverse effects, with unaltered neuroprotective potency.

KW - Antiapoptotic activity

KW - Dopamine potentiation

KW - MAO-B

KW - Neurodegenerative diseases

KW - R-(-)-deprenyl

KW - Selegiline

UR - http://www.scopus.com/inward/record.url?scp=3242762403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3242762403&partnerID=8YFLogxK

M3 - Article

VL - 11

SP - 2017

EP - 2031

JO - Current Medicinal Chemistry

JF - Current Medicinal Chemistry

SN - 0929-8673

IS - 15

ER -