Deprenyl - Selegiline

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

A final pharmacological strategy for treatment of Parkinson s disease comes from enzyme inhibition. This was initally done with an MAO inhibitor, L-deprenyl (selegiline, Eldepryl), but more recent drugs have become available that are COMT inhibitors. L-Deprenyl is an inhibitor of MAOB, which is the form of MAO selective to dopamine. Thus, it may increase the amount of available dopamine for release. Second, it may protect dopamine neurons by reducing the oxidative stress concomitant with dopamine metabolism (Olanow 1997). Third, L-deprenyl is metabolized into amphetamine and methamphetamine, which may contribute to their antiparkinsonian effects. Unlike other treatments for Parkinson s disease, L-deprenyl seems to slow the progression of the disease. Tolcapone (Tasmar) is a COMT inhibitor, which prevents extracellular breakdown of dopamine. 

L-deprenyl (selegiline), a monoamine oxidase B inhibitor, clonidine and guanfacine, a2-adreno-receptor agonists, and levodopa (L-dopa) have been reported to improve cognitive function in some subjects. Zimeldine, citaloprani, and alaproclate — selective serotonin uptake blockers — have no beneficial effects. 

Knoll J. Rationale for (-)deprenyl (selegiline) medication in Parkinson s disease and in prevention of age-related nigral changes. Biomed Pharmacother 1995 49 187-195. 

Tetrud JW, Langston JW (1989) The effect of deprenyl (selegiline) on the natural history of Parkinson s disease. Science 245 519-522. 

Figure 12.3. Phenylpiperidine analgesics and metabolic activation of MPTP. In efforts to synthesize the meperidine-like analgesic agent MPPP ("designer heroin,") (4), MPTP (3)can be formed. It is converted selectively by monoamine oxidase type B (MAO-B, inhibited by agents including deprenyl (selegiline)and pargylineto MPDP (7), and thence to MPP" (8)the proposed toxic species that accumulated in dopamine neurons to result in disruption of their cellular respiration and death.

Deprenyl (Selegiline) and / -(-)-1-(benzofuran-2-yl)-2-propylaminopentane [H-BPAP], Prototypes of Synthetic Mesencephalic Enhancer Substances... 

Deprenyl (Selegiline), developed in the early 1960s as a new spectrum psychostimulant and potent MAO inhibitor, later proved to be, as the first selective inhibitor of MAO-B, indispensable for investigating the nature and function of B-type MAO. Hundreds of clinical studies with the drug were designed thereafter in the firm belief that selective blockade of MAO-B was responsible... 

Knoll J (1986c) Role of B-type monoamine oxidase inhibition in the treatment of Parkinson s disease. An update. In Shah NS, Donald AG (eds) Movement disorders. Plenum Press, New York, pp 53-81 Knoll J (1987) / -(-) Deprenyl (Selegiline, Movergan ) facilitates the activity of the nigrostriatal dopaminergic neuron. J Neural Transm 25 45-66 Knoll J (1988) The striatal dopamine dependency of lifespan in male rats. 

Miklya I, Knoll J (2003) Analysis of the effect of (-)-BPAP, a selective enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain. life Sci 72 2915-2921 Miklya I, Knoll B, Knoll J (2003a) A pharmacological analysis elucidating why, in contrast to (-)-deprenyl (selegiline) a-tocopherol was ineffective in the DATATOP study. Life Sci 72 2641-2648... 

Heinonen E, Anttila M, Lammintausta A. Pharmacokinetic aspects of 1-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther 1994 56 742-749. 

MAOIs can be classified into two groups the irreversible (older) MAOIs such as Parnate (tranylcypromine) and Nardil (phenelzine), and the reversible (newer) drugs such as Manerix (moclobemide) and Deprenyl (selegiline). Older MAOIs have more side effects associated with them since their action is less specific than newer MAOIs. 

L-Deprenyl (Selegiline ), a selective monoamine oxidase-B inhibitor, in the treatment of early Parkinson s disease... 

Knoll, J. (1987) (-)Deprenyl (Selegiline, Movergan) facilitates the activity of the nigrostriatal dopaminergic neuron, J. Neural. Transm. 25 (Suppl.) 45-66. 

Knoll, J. (1992b) The pharmacological profile of (-)deprenyl (Selegiline) and its relevance for humans a personal view. Pharmacol. Toxicol. 70 317-321. 

Knoll j. ( )Deprenyl (selegiline) past, present and future. Neurobiology 2000 8 179-199. 

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