Pharmacology Selegiline

1 pharmacology

1.1 protein binding
1.2 pharmacokinetics of pill form
1.3 pharmacokinetics of patch form
1.4 metabolites

1.4.1 desmethylselegiline
1.4.2 levoamphetamine , levomethamphetamine

pharmacology
protein binding

selegiline selective inhibitor of mao-b; mao-b metabolizes dopamine , phenylethylamine.

selegiline inhibits cyp2a6 , can increase effects of nicotine result. selegiline appears activate σ1 receptors relatively high affinity of approximately 400 nm.

pharmacokinetics of pill form

selegiline has low oral bioavailability, increases moderate when ingested high-fat meal, molecule being fat soluble.

selegiline s oral bioavailability drastically increased in females taking oral contraceptives (10- 20-fold). lead loss of mao-b selectivity, inhibition of both mao-a , mao-b, make patients susceptible usual risks of unselective maois such tyramine-induced hypertensive crisis , serotonin toxicity when combined serotonergics such ssris.

pharmacokinetics of patch form

following application of patch humans, 25% 30% of selegiline content on average delivered systemically on 24 hours (range approximately 10% 40%). transdermal dosing results in higher exposure selegiline lower exposure metabolites when compared oral dosing, due extensive first-pass metabolism pill form , low first-pass metabolism patch form. site of application not significant factor in how drug distributed. in humans, selegiline not accumulate in skin nor metabolized in skin.

when radiolabeled selegiline given transdermally laboratory animals, drug rapidly distributed body tissues , rapidly penetrates blood–brain barrier.

metabolites
desmethylselegiline

n-desmethylselegiline may have neuroprotective antiapoptotic properties. large multicenter study suggests decrease in disease progression of parkinsonism may have reflected other symptomatic response. desmethylselegiline metabolized cyp2c19.

levoamphetamine , levomethamphetamine

selegiline partly metabolized levomethamphetamine (l-methamphetamine), 1 of 2 enantiomers of methamphetamine, in vivo. while these metabolites may contribute drug s ability inhibit reuptake of neurotransmitters dopamine , norepinephrine, have been associated orthostatic hypotension , hallucinations in people. newer antiparkinson mao-b inhibitor, rasagiline, metabolizes 1(r)-aminoindan has no amphetamine-like characteristics.

this metabolic pathway may cause persons taking selegiline test positive amphetamine or methamphetamine on drug screening tests.