They cross the blood–brain barrier and enter the brain, where they most concentrated at the thalamus, basal ganglia, midbrain, and cingulate gyrus.Selegiline is mostly metabolized in the intestines and liver; it and its metabolites are excreted in the urine.Buccal administration of selegiline results in 5-fold higher bioavailability, more reproducible blood concentration, and produces less amphetamine metabolites than the oral tablet form. Metabolism
Selegiline is metabolized by cytochrome P450 to L-desmethylselegiline and levomethamphetamine. Desmethylselegiline has some activity against MAO-B, but much less than that of selegiline. It is thought to be further metabolized by CYP2C19. Levomethamphetamine (the less potent of the two enantiomers of methamphetamine) is converted to levoamphetamine (the less potent of the two enantiomers of amphetamine, with regards to psychological effects). Due to the presence of these metabolites, people taking selegiline may test positive for "amphetamine" or "methamphetamine" on drug screening tests. While the amphetamine metabolites may contribute to selegilines ability to inhibit reuptake of the neurotransmitters dopamine and norepinephrine, they have also been associated with orthostatic hypotension and hallucinations. The amphetamine metabolites are hydroxylated and, in phase II, conjugated by glucuronyltransferase. A newer anti-Parkinson MAO-B inhibitor, rasagiline, metabolizes into 1(R)-aminoindan, which has no amphetamine-like characteristics. Patch
Following application of the patch to humans, an average of 25% to 30% of the selegiline content is delivered systemically over 24 hours.
Though it is labeled for dog use only, selegiline has been used off-label for geriatric cats with cognitive dysfunction.Selegilines efficacy in treating pituitary-dependent hyperadrenocorticism has been disputed. Theoretically, it works by increasing dopamine levels, which downregulates the release of ACTH, eventually leading to reduced levels of cortisol. Some claim that selegiline is only effective at treating PDH caused by lesions in the anterior pituitary (which comprise most canine cases). The greatest sign of improvement is lessening of abdominal distention.Side effects in dogs are uncommon, but they include vomiting, diarrhea, diminished hearing, salivation, decreased weight and behavioral changes such as hyperactivity, listlessness, disorientation, and repetitive motions.Selegiline does not appear to have a clinical effect on horses. Research
Selegiline has been limitedly studied in the treatment of attention deficit hyperactivity disorder (ADHD) in both children/adolescents and adults. In a small randomized trial of selegiline for treatment of ADHD in children, there were improvements in attention, hyperactivity, and learning/memory performance but not in impulsivity. In another small randomized controlled trial of selegiline for the treatment of adult ADHD, a high dose of the medication for 6 weeks was not significantly more effective than placebo in improving symptoms. == References ==