For substituted amphetamines - lipophilic character and MAO-A

[Simfish]

For substituted amphetamines, what is responsible for the positive correlation between the the lipophilic character of a para-substituent, and the ability of molecule to inhibit monoamine oxidase?

Additionally, how significant of a role does the inhibition of MAO play in the increase of extracellular dopamine concentrations compared to the molecule's competitive inhibition of dopamine reuptake, or its properties as a dopamine releasing agent?

 

[sekio]

1. See http://www.sciencedirect.com/science/article/pii/S000629529700405X ...

The analysis of structure–activity relationships indicates that: molecules with amphetamine-like structure and different substitutions on the aromatic ring are potentially MAO-A inhibitors; substituents at different positions of the aromatic ring modify the potency but have little influence on the selectivity; substituents at the para position such as amino, alkoxyl, halogens, or alkylthio produce a significant increase in the activity; the para-substituent must be an electron donor; bulky groups next to the para substituent lead to a decrease in the activity; substituents located at positions more distant on the aromatic ring have less influence and, even when the substituent is a halogen (Cl, Br), an increase in the activity of the compound is obtained.

2. Negligible (http://www.bluelight.ru/vb/threads/...acology-Text?p=3473367&viewfull=1#post3473367)

 

[Simfish]

Wow nice - thanks very much for the reply!