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Novel Phenethylamines and their Potential Interactions with Prescription Drugs: A Systematic Critical Review.

PURPOSE
The novel phenethylamines 4-fluoroamphetamine (4-FA) and 2,5-dimethoxy-4-bromophenethylamine (2C-B), fall in the top 10 most used new psychoactive substances (NPS) amongst high-risk substance users. Various phenethylamines and NPS are also highly used in populations with mental disorders; depression or attention deficit hyperactivity disorder (ADHD). Moreover, NPS use is highly prevalent among men and women with risky sexual behavior. Considering these specific populations and their frequent concurrent use of drugs like antidepressants, ADHD medication, and antiretrovirals, reports on potential interactions between these drugs, and phenethylamines 4-FA and 2C-B, were reviewed.


METHODS
The authors performed a systematic literature review on 4-FA and 2C-B interactions with antidepressants (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, bupropion, venlafaxine, phenelzine, moclobemide, and tranylcypromine), ADHD medications (atomoxetine, dexamphetamine, methylphenidate, and modafinil), and antiretrovirals.


RESULTS
Limited literature exists on the pharmacokinetics and drug-drug interactions of 2C-B and 4-FA. Only one case report indicated a possible interaction between 4-FA and ADHD medication. Although pharmacokinetic interactions between 4-FA and prescription drugs remain speculative, their pharmacodynamics points towards interactions between 4-FA and ADHD medication and antidepressants. The pharmacokinetic and pharmacodynamic profile of 2C-B, also points towards such interactions; between 2C-B and prescription drugs like antidepressants and ADHD medication.


CONCLUSION
A drug-drug (phenethylamine-prescription drug) interaction potential is anticipated, mainly involving monoamine oxidases for 2C-B and 4-FA, with monoamine transporters being more specific to 4-FA.