Pharmacology of selegiline

Pharmacology of selegiline
Clinical data
Routes of
administration		• Oral (tablet, capsule)[1][2]
• Buccal (ODTTooltip orally disintegrating tablet)[3][4]
• Transdermal (patch)[5][6]
Drug classMonoamine oxidase inhibitor; Catecholaminergic activity enhancer; Norepinephrine releasing agent; Antiparkinsonian; Antidepressant; Neuroprotective
Pharmacokinetic data
BioavailabilityOral: 4–10%[2][7][8]
ODT: ~5–8× oral[9][4][10]
Patch: 75%[6]
Protein binding85–90%[6][5][3]
MetabolismLiver, other tissues (CYP2B6, CYP2C19, others)[2][14][6][15]
Metabolites• Desmethylselegiline (DMS)
• Levomethamphetamine (L-MA)
• Levoamphetamine (L-A)
Elimination half-lifeOral:
• S (single): 1.2–3.5 h[2]
• S (multi): 7.7–9.7 h[2][8]
• DMS (single): 2.2–3.8 h[2]
• DMS (multi): 9.5 h[2]
• L-MA: 14–21 h[2][4]
• L-A: 16–18 h[2][4]
ODT:
• S (single): 1.3 h[3]
• S (multi): 10 h[3]
Patch:
• S: 20 h[8][5]
ExcretionUrine (87%):[11][12][4][2][13]
• L-MA: 20–63%
• L-A: 9–26%
• DMS: 1%
• S: 0.01–0.03%
Feces: 15%[11][4]

The pharmacology of selegiline is the study of the pharmacodynamic and pharmacokinetic properties of the antiparkinsonian and antidepressant selegiline (L-deprenyl). Selegiline is available in a few different forms, including oral tablets and capsules, orally disintegrating tablets (ODTs), and transdermal patches. These forms have differing pharmacological properties.

In terms of pharmacodynamics, selegiline acts as a monoamine oxidase (MAO) inhibitor. It is a selective inhibitor of monoamine oxidase B (MAO-B) at lower doses but additionally inhibits monoamine oxidase A (MAO-A) at higher doses. MAO-B inhibition is thought to result in increased levels of dopamine, whereas MAO-A inhibition results in increased levels of serotonin, norepinephrine, and dopamine. Selegiline is also a catecholaminergic activity enhancer (CAE) and enhances the action potential-evoked release of norepinephrine and dopamine. Through its active metabolites levomethamphetamine and levoamphetamine, selegiline acts as a weak norepinephrine and/or dopamine releasing agent. The clinical significance of this action is unclear, but it may be relevant to the effects and side effects of selegiline, especially at higher doses.

With regard to pharmacokinetics, the bioavailability of the oral form is 4 to 10%, of the ODT is 5 to 8 times that of the oral form, and of the transdermal patch is 75%. The plasma protein binding of selegiline is 85 to 90%. It is metabolized extensively in the liver by the cytochrome P450 enzyme CYP2B6 among other enzymes. Metabolites of selegiline include desmethylselegiline (DMS), levomethamphetamine, and levoamphetamine. The oral form of selegiline is subject to strong first-pass metabolism and levels of the metabolites of selegiline are much lower with the ODT and transdermal patch forms than with the oral form. The elimination half-lives of selegiline and its metabolites range from 1.2 to 10 hours for selegiline, 2.2 to 9.5 hours for DMS, 14 to 21 hours for levomethamphetamine, and 16 to 18 hours for levoamphetamine. Selegiline and its metabolites are eliminated mainly in urine, with its metabolites accounting for the vast majority of eliminated material in the case of the oral form.

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