A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), α-tocopherol was ineffective in the DATATOP study

I. Miklya, B. Knoll, J. Knoll

Research output: Contribution to journalArticle

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Abstract

The Parkinson Study Group who conducted the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial designed their study in the belief that the MAO inhibitor (-)-deprenyl (selegiline), the antioxidant α-tocopherol, and the combination of the two compounds will slow the clinical progression of the disease to the extent that MAO activity and the formation of oxygen radicals contribute to the pathogenesis of nigral degeneration. In fact, (-)-deprenyl only delayed the onset of disability associated with early, otherwise untreated Parkinson's disease, however, in contrast to the expectation of the authors, α-tocopherol proved to be ineffective in the DATATOP study. Enhancer substances, (-)-deprenyl, (-)-1-phenyl-2-propylaminopentane [(-)-PPAP] the (-)-deprenyl analogue free of MAO inhibitory potency, and R-(-)1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] the presently known most potent enhancer substance, are peculiar stimulants. They enhance the impulse propagation mediated release of the catecholamines in the brain. Due to their enhancer effect, the amount of catecholamines released from selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus) is significantly higher in rats treated with an enhancer substance than in saline treated rats. We compared the effect of (-)-deprenyl 0.025 and 0.25 mg/kg, (-)-PPAP 0.1 mg/kg, (-)-BPAP 0.0001 mg/kg, and α-tocopherol 25 and 50 mg/kg, in this test. The doses of (-)-deprenyl and α-tocopherol were selected to be in compliance with the dose given in the DATATOP study. Compared to saline treated rats, the enhancer substances significantly increased the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium and the amount of norepinephrine released from the locus coeruleus; α-tocopherol was ineffective. The results indicate that α-tocopherol was ineffective, because, unlike (-)-deprenyl it dose not enhance the activity of the nigrostriatal dopaminergic neurons.

Original languageEnglish
Pages (from-to)2641-2648
Number of pages8
JournalLife Sciences
Volume72
Issue number23
DOIs
Publication statusPublished - Apr 25 2003

Fingerprint

Selegiline
Tocopherols
Parkinsonian Disorders
Pharmacology
Substantia Nigra
Therapeutics
Rats
Locus Coeruleus
Monoamine Oxidase
Catecholamines
Brain
Monoamine Oxidase Inhibitors
Dopaminergic Neurons
Neurons
Parkinson Disease
Disease Progression
Reactive Oxygen Species
Dopamine
Norepinephrine
Antioxidants

Keywords

  • α-tocopherol
  • β-phenylethylamine (PEA)
  • (-)-1-phenyl-2-propylaminopentane [(-)-PPAP]
  • (-)-deprenyl (selegiline)
  • DATATOP study, Parkinson's disease
  • Enhancer compounds
  • Enhancer effect
  • R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP]

ASJC Scopus subject areas

  • Pharmacology

Cite this

A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline), α-tocopherol was ineffective in the DATATOP study. / Miklya, I.; Knoll, B.; Knoll, J.

In: Life Sciences, Vol. 72, No. 23, 25.04.2003, p. 2641-2648.

Research output: Contribution to journalArticle

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