Selegiline is an irreversible monoamine oxidase (MAO) inhibitor typically used in the treatment of Parkinson’s disease. Monoamine oxidase A (MAO-A) generally metabolizes tyramine, norepinephrine, serotonin, and dopamine, whereas in comparison, monoamine oxidase B (MAO-B) metabolizes mostly dopamine (Youdim, Edmondson, & Tipton, 2006). Following conversion by MAO to its active form, selegiline inactivates MAO by irreversible binding to MAO-B. The differences between the selectivity of the two enzymes should be utilized in treating specific disorders. Despite widespread recognition of MAOI efficacy in treatment of depression, the necessity for dietary restriction leaves these drugs less desired. As discussed in the article by Azzaro et al. (2006),
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This is problematic considering the anti-depressant dose does not preserve the selective inhibition of MAO-B within the periphery and can lead to a dramatic increase in blood pressure following the consumption of tyramine rich food. Selective MAO-B inhibition is not currently linked to antidepressant activity, however, selective MAO-B inhibitors bypass this issue by preferentially inhibiting MAO-B. MAO-B inhibition means there will be more dopamine available for proper neuronal functioning (Azzaro et al., 2006; Yamada & Yasuhara, 2004). To overcome these problems, the selegiline transdermal system (STS), was developed. Its novel pharmacokinetic and pharmacodynamic properties are thought to allow for increased amounts of the drug delivered to the brain and decreased metabolite production. Additionally, STS allows for the targeted inhibition of central nervous system MAO-A and MAO-B isoenzymes with minimal effects on MAO-A in the gastrointestinal and liver systems, which reduces the risk of interactions with tyramine-rich foods (Azzaro et al., …show more content…
These results alongside results from clinical trials show transdermal delivery of selegiline via the STS 6mg/24h to demonstrate superior antidepressant efficacy and tolerability to placebo treatment, making it an option for those in need of the therapeutic intervention. Healthy male subjects were challenged with capsules of tyramine HCl under various conditions. In one group treated with STS 6 mg/24 hours for 9 days and then 33 days (with a 3 month washout period between treatments), the mean tyramine pressor doses in the absence of food, at 9 and 33 days were 292 mg and 204 mg, respectively (p < 0.05). Although there is statistical significance, there is no clinical implication in safety noted. Ingestion of tyramine at 200 mg or more, derived from a single meal, is extremely unlikely and roughly 6 times more than that contained in a tyramine-rich meal and 20 times greater than that contained in a normal meal.
The pharmacokinetics differ between the two routes of administration enough that the data provides the basis for therapeutic advantages of the selegiline transdermal system in administering antidepressant doses of selegiline. Though while not necessarily possible in human trials, it would be beneficial to see
This is problematic considering the anti-depressant dose does not preserve the selective inhibition of MAO-B within the periphery and can lead to a dramatic increase in blood pressure following the consumption of tyramine rich food. Selective MAO-B inhibition is not currently linked to antidepressant activity, however, selective MAO-B inhibitors bypass this issue by preferentially inhibiting MAO-B. MAO-B inhibition means there will be more dopamine available for proper neuronal functioning (Azzaro et al., 2006; Yamada & Yasuhara, 2004). To overcome these problems, the selegiline transdermal system (STS), was developed. Its novel pharmacokinetic and pharmacodynamic properties are thought to allow for increased amounts of the drug delivered to the brain and decreased metabolite production. Additionally, STS allows for the targeted inhibition of central nervous system MAO-A and MAO-B isoenzymes with minimal effects on MAO-A in the gastrointestinal and liver systems, which reduces the risk of interactions with tyramine-rich foods (Azzaro et al., …show more content…
These results alongside results from clinical trials show transdermal delivery of selegiline via the STS 6mg/24h to demonstrate superior antidepressant efficacy and tolerability to placebo treatment, making it an option for those in need of the therapeutic intervention. Healthy male subjects were challenged with capsules of tyramine HCl under various conditions. In one group treated with STS 6 mg/24 hours for 9 days and then 33 days (with a 3 month washout period between treatments), the mean tyramine pressor doses in the absence of food, at 9 and 33 days were 292 mg and 204 mg, respectively (p < 0.05). Although there is statistical significance, there is no clinical implication in safety noted. Ingestion of tyramine at 200 mg or more, derived from a single meal, is extremely unlikely and roughly 6 times more than that contained in a tyramine-rich meal and 20 times greater than that contained in a normal meal.
The pharmacokinetics differ between the two routes of administration enough that the data provides the basis for therapeutic advantages of the selegiline transdermal system in administering antidepressant doses of selegiline. Though while not necessarily possible in human trials, it would be beneficial to see