Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain

J. S. Fowler, N. D. Volkow, J. Logan, D. Franceschi, G. J. Wang, R. MacGregor, C. Shea, V. Garza, N. Pappas, P. Carter, N. Netusil, P. Bridge, D. Liederman, A. Elkashef, J. Rotrosen, Robert Hitzemann

Research output: Contribution to journalArticle

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Abstract

In this study, we investigated whether treatment with L-deprenyl, a selective monoamine oxidase B (MAO B) inhibitor, also inhibits MAO A or the dopamine transporter in the human brain. Six normal volunteers (age 46±6 yrs) had two PET sessions, one at baseline and one following L-deprenyl (10 mg/day) for 1 week. Each session included one scan with [11C]clorgyline (to assess MAO A) and one scan 2 hours later with [11C]cocaine (to assess dopamine transporter availability). A 3-compartment model was used to compare the plasma-to-brain transfer constant, K1 (a function of blood flow) and λk3 (a kinetic term proportional to brain MAO A) before and after treatment. Dopamine transporter availability was measured as the ratio of distribution volumes of the striatum to cerebellum (DVR) which is equal to Bmax/KD + 1. L-Deprenyl treatment for 1 week did not affect either brain MAO A activity or dopamine transporter availability. There was a non-significant trend for an increase in K1 after L-deprenyl. These results confirm that L-deprenyl after one week of treatment at doses typically used clinically is selective for MAO B and that it does not produce a measurable affect on the dopamine transporter, suggesting that MAO A inhibition and dopamine transporter blockade do not contribute to its pharmacological effects.

Original languageEnglish (US)
Pages (from-to)2759-2768
Number of pages10
JournalLife Sciences
Volume68
Issue number24
DOIs
StatePublished - May 4 2001
Externally publishedYes

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Selegiline
Dopamine Plasma Membrane Transport Proteins
Monoamine Oxidase
Brain
Availability
Therapeutics
Clorgyline
Monoamine Oxidase Inhibitors
Cocaine
Cerebellum
Healthy Volunteers
Blood
Pharmacology
Plasmas
Kinetics

Keywords

  • Dopamine transporter
  • L-Deprenyl
  • Monoamine oxidase A

ASJC Scopus subject areas

  • Pharmacology

Cite this

Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain. / Fowler, J. S.; Volkow, N. D.; Logan, J.; Franceschi, D.; Wang, G. J.; MacGregor, R.; Shea, C.; Garza, V.; Pappas, N.; Carter, P.; Netusil, N.; Bridge, P.; Liederman, D.; Elkashef, A.; Rotrosen, J.; Hitzemann, Robert.

In: Life Sciences, Vol. 68, No. 24, 04.05.2001, p. 2759-2768.

Research output: Contribution to journalArticle

Fowler, JS, Volkow, ND, Logan, J, Franceschi, D, Wang, GJ, MacGregor, R, Shea, C, Garza, V, Pappas, N, Carter, P, Netusil, N, Bridge, P, Liederman, D, Elkashef, A, Rotrosen, J & Hitzemann, R 2001, 'Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain', Life Sciences, vol. 68, no. 24, pp. 2759-2768. https://doi.org/10.1016/S0024-3205(01)01079-7
Fowler, J. S. ; Volkow, N. D. ; Logan, J. ; Franceschi, D. ; Wang, G. J. ; MacGregor, R. ; Shea, C. ; Garza, V. ; Pappas, N. ; Carter, P. ; Netusil, N. ; Bridge, P. ; Liederman, D. ; Elkashef, A. ; Rotrosen, J. ; Hitzemann, Robert. / Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain. In: Life Sciences. 2001 ; Vol. 68, No. 24. pp. 2759-2768.
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