Selegiline (Deprenyl, Emsam) is a medical drug that acts as a selective, irreversible monoamine oxidase inhibitor (MAOI). It is selective for MAO-B at low doses, but loses its selectivity at higher doses. It exists as an oral formulation as well as a transdermal patch.
Introduction to Selegiline
Selegiline is a medication used to treat symptoms of Parkinson's disease. Since the introduction of a transdermal formulation of selegiline, it is also being used more frequently to treat depression. For this indication, it is usually prescribed after more common antidepressants have failed, but before putting a patient on one of the irreversible and non-selective MAOIs, such as tranylcypromine or phenelzine. Selegiline is also used off-label as a nootropic and neuroprotective agent.
Pharmacology of Selegiline
LD50 (mg/kg) :
Rat : 385 orally, 63 intravenously, 126 subcutaneously (racemate hydrochloride)
Rat : 81 intravenously, 280 subcutaneously (hydrochloride)
Selegiline is metabolized in the liver to (–)-desmethylselegiline and (–)-methamphetamine. Desmethylselegiline irreversibly inhibits the action of Monoamine oxidase B which is responsible for metabolizing dopamine. Selegiline also prevents reuptake of dopamine and increases dopamine release. By these mechanisms Selegiline increase dopamine levels and decreases symptoms present in people with Parkinsons.
In cases of Parkinsons disease there is extensive dopaminergic cell death in the substantia nigra. Activation of glutamate receptors causes an increase in intracellular Ca2+ which activates protease and phospholipase A2. By regular metabolic processes these enzymes cause an accumulation of free radicals. Glutathione (GSH) is an endogenous antioxidant that is responsible for preventing damage to the cell by oxygen radicals. When buthionine sulfoximine (BSO) was administered (10 μM) it significantly depleted GSH levels and caused dopamine-induced apoptosis. Selegiline has been shown to protect against BSO induced toxicity even when GSH levels are low.[1]
Endogenously produced N-methylated isoquinolines are a group of neurotoxic compounds that can damage dopaminergic cells via oxidative stress. MAO B produces free radicals when isoquinolines are oxidized. Another compound that has been studied extensively is MPTP, which is oxidized into MPP+ which in turn accelerates dopaminergic cell death. Inhibiting the action of MAO B, Selegiline has been shown to block the neurotoxic effect of these free radical compounds.[1]
Chemistry of Selegiline
[2]
Column 1 Column 2 Systematic(IUPAC) name: ([alpha]R)-N,[alpha]-Dimethyl-N-2-propyn-1-ylbenzeneethanamine Synonyms: L-(-)-N,[alpha]-Dimethyl-N-2-propynylphenethylamine, L-N-(2-phenylisopropyl)-N-methylprop-2-ynylamine, (-)-deprenyl, L-deprenyl, Emsam; Anipryl, Antiparkin, Amindan, Carbex, Déprényl, Egibren, Eldepryl, Jumex, Movergan, Otrasel, Plurimen, Seledat, Selegam, Selepark, Selgimed, Xilopar, Zelapar (hydrochloride); Deprenyl, phenylisopropyl-N-methylpropynylamine (racemate); E-250 (racemate hydrochloride) Molecular Formula: C13H17N Molar mass: 187.29 g/mol, 223.74 g/mol (hydrochloride) CAS Registry Number: 14611-51-9, 14611-52-0 (hydrochloride), 2323-36-6 (racemate), 2079-54-1 (racemate hydrochloride) Melting Point: 141-142°C (hydrochloride), 131-131.5°C (racemate hydrochloride, crystals from ethanol-ether) Boiling Point: 92-93°C @ 0.8 mmHg, 104-110°C @ 5mmHg (racemate) Flash Point: no data Solubility: Hydrochloride freely soluble in water, chloroform, methanol Additionnal data: none Notes: Freebase as an oil, racemate crystallyzed from ethanol-ether
The dangers of Selegiline
Selegiline is safe to use in doses of 10mg per day and does not cause hypertension when tryramine containing foods are consumed. It can be combined with citalopram or cabergoline (Ebadi et al., 2002).[1]
More Selegiline Sections
Selegiline experiences - Post & read experiences with Selegiline. Nootropics forum - Post and read about Selegiline.