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  • Title: R-(-)-deprenyl (Selegiline, Movergan) facilitates the activity of the nigrostriatal dopaminergic neuron.
    Author: Knoll J.
    Journal: J Neural Transm Suppl; 1987; 25():45-66. PubMed ID: 2828537.
    Abstract:
    (-)Deprenyl, when administered continuously in small doses (0.25 mg/kg/day), facilitates the activity of the nigrostriatal dopaminergic neuron because of its highly characteristic complex spectrum of pharmacologic activity: it is a highly potent and selective inhibitor of B-type MAO; it inhibits the reuptake of dopamine; it inhibits dopamine autoreceptors; it enhances scavenger function. 1) (-)Deprenyl treatment decreased significantly the activity of the cholinergic interneurons. In a series of experiments the acetylcholine (ACh) content was found to be 0.69 nmole/mg protein in the striatum of untreated rats, whereas a significantly higher amount of ACh (0.86 nmol/mg protein) was found in the rat striatum after two week pretreatment with (-)deprenyl, and the fractional rate constant (kb) of ACh efflux from the cholinergic interneurons of the striatum decreased significantly in the (-)deprenyl-treated group from 9.1 +/- 0.8 to 6.2 +/- 0.55. 2) The (-)deprenyl-induced increase of the dopaminergic tone in the striatum was proved by measurements of the activity of the nigrostriatal dopaminergic neuron. Whereas the striatum of untreated rats contained 52.7 +/- 1.6 nmole/g dopamine (DA) and the turnover rate (TRDA) was found to be 13.7 +/- 1.3 nmole/g/hr, the striatum of rats pretreated with 0.25 mg/kg (-)deprenyl daily for 28 days contained significantly higher amount of DA (81.77 +/- 5.7 nmole) and the turnover rate increased significantly to 24.44 +/- 1.1. Using the Glowinski-Iversen preparation we found that from the striata of untreated rats 200.0 +/- 25.8 pmole/g/min DA was released to KCl stimulation, whereas the amount of DA released to stimulation from the striata of rats pretreated with (-)deprenyl for 3 weeks increased significantly to 1452.2 +/- 183.1 pmole/g/min. 3) (-)Deprenyl inhibits the uptake of dopamine into the nigrostriatal dopaminergic neuron. In a new series of experiments we found that 420 +/- 21 pmole/g protein 3H-DA was taken up within 5 minutes in the striatum slices of untreated rats. Pretreatment of the rats with 0.25 mg/kg (-)deprenyl daily for two weeks decreased significantly the uptake of DA to 284 +/- 28 pmole/mg. 4) In a new series of experiments we found that the striata of untreated rats emitted 404.2 +/- 36.2 pmole/g/min ACh to ouabain stimulation but the striata dissected from rats pretreated with 6-hydroxy-dopamine (6-OHDA) released 811.4 +/- 49.2 pmol/g/min (p less than or equal to 0.001).
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