Pharmacodynamics<unk>  is a non-selective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It inhibits both of the respective isoforms of MAO, MAO-A and MAO-B, and does so almost equally, with slight preference for the former. By inhibiting MAO,<unk>  prevents the breakdown of the monoamine neurotransmitters serotonin, melatonin, norepinephrine, epinephrine, and dopamine, as well as the trace amine neuromodulators such as phenethylamine, tyramine, octopamine, and tryptamine. This leads to an increase in the extracellular concentrations of these neurochemicals and therefore an alteration in neurochemistry and neurotransmission. This action is thought to be the primary mediator in<unk> 's therapeutic benefits.<unk>  and its metabolites also inhibit at least two other enzymes to a lesser extent, of which are alanine transaminase (ALA-T), and γ-aminobutyric acid transaminase (GABA-T), the latter of which is not caused by<unk>  itself, but by a<unk>  metabolite phenylethylidenehydrazine (PEH). By inhibiting ALA-T and GABA-T,<unk>  causes an increase in the alanine and GABA levels in the brain and body. GABA is the major inhibitory neurotransmitter in the mammalian central nervous system, and is very important for the normal suppression of anxiety, stress, and depression.<unk> 's action in increasing GABA concentrations may significantly contribute to its antidepressant, and especially, anxiolytic/antipanic properties, the latter of which have been considered superior to those of other antidepressants. As for ALA-T inhibition, though the consequences of disabling this enzyme are currently not well understood, there is some evidence to suggest that it is this action of the hydrazines (including<unk>  which may be responsible for the occasional incidence of hepatitis and liver failure.<unk>  has also been shown to metabolize to phenethylamine (PEA). PEA acts as a releasing agent of norepinephrine and dopamine, and this occurs in the same manner as amphetamine (very similar in structure) by being taken up into vesicles, and displacing, and causing the release of those monoamines (though with markedly different pharmacokinetics such as a far shorter duration of action). Although this is indeed the same mechanism to which some (but not all) of amphetamine's effects are attributable to, this is not all that uncommon a property among phenethylamines in general, many of which do not have psychoactive properties comparable to amphetamine. Amphetamine is different in that it binds with high affinity to the reuptake pumps of dopamine, norepinephrine, and serotonin, which phenethylamine and related molecules may as well to some extent, but with far less potency, such that it is basically insignificant in comparison. And, often being metabolized too quickly or not having the solubility to enable it to have a psychostimulant effect in humans. Claims that phenethylamine has comparable or roughly similar effects to psychostimulants such as amphetamine when administered are misconstrued. Phenethylamine does not have any obvious, easily discernible, reliably induced effects when administered to humans.<unk> 's enhancement of PEA levels may contribute further to its overall antidepressant effects to some degree. In addition, phenethylamine is a substrate for MAO-B, and treatment with MAOIs that inhibit MAO-B such as<unk>  have been shown to consistently and significantly elevate its concentrations.<unk>  usually requires six to eight weeks of treatment, and a minimum dose of 60 mg/day, to achieve therapeutic effects. The reason for the delay in therapeutic effect is not fully understood, but it is believed to be due to many factors, including achieving steady-state levels of MAO inhibition and the resulting adaptations in mean neurotransmitter levels, the possibility of necessary desensitization of autoreceptors which normally inhibit the release of neurotransmitters like serotonin and dopamine, and also the upregulation of enzymes such as serotonin N-acetyltransferase. Typically, a therapeutic response to MAOIs is associated with an inhibition of at least 80-85% of monoamine oxidase activity. Pharmacokinetics<unk>  15 mg tablets.<unk>  is administered orally in the form of<unk>  sulfate and is rapidly absorbed from the gastrointestinal tract. Time to peak plasma concentration is 43 minutes and half-life is 11.6 hours. Unlike most other drugs,<unk>  irreversibly disables MAO, and as a result, it does not necessarily need to be present in the blood at all times for its effects to be sustained. Because of this, upon<unk>  treatment being ceased, its effects typically do not actually wear off until the body replenishes its enzyme stores, a process which can take as long as 2–3 weeks.<unk>  is metabolized primarily in the liver and its metabolites are excreted in the urine. Oxidation is the primary routine of metabolism, and the major metabolites are phenylacetic acid and parahydroxyphenylacetic acid, recovered as about 73% of the excreted dose of<unk>  in the urine over the course of 96 hours after single doses. Acetylation to N2-acetylphenelzine is a minor pathway.<unk>  may also interact with cytochrome P450 enzymes, inactivating these enzymes through formation of a heme adduct. Two other minor metabolites of<unk> , as mentioned above, include phenylethylidenehydrazine and phenethylamine.
Phenelzine
Nabilone
Hydroxyzine
Chloracyzine
Naltrexone
Fluparoxan
Citalopram
Medazepam