Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain.
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 lambdak3 (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.
Fowler
J S
JS
Brookhaven National Laboratory, Upton, NY 11973, USA. fowler@bnl.gov
Volkow
N D
ND
Logan
J
J
Franceschi
D
D
Wang
G J
GJ
MacGregor
R
R
Shea
C
C
Garza
V
V
Pappas
N
N
Carter
P
P
Netusil
N
N
Bridge
P
P
Liederman
D
D
Elkashef
A
A
Rotrosen
J
J
Hitzemann
R
R
D000328:Adult; D001921:Brain / Q000187:drug effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003010:Clorgyline / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D012642:Selegiline / Q000494:pharmacology*
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D012642:Selegiline; D003010:Clorgyline