(±)-Amiflamine

Amiflamine was 3 times less potent within noradrenergic neurons than within serotonergic neurons. A brain to plasma ratio of about 20:1 was found for amiflamine and its metabolites. The plasma and the brain concentrations of the N-demethylated metabolite [FLA 788(+)] exceeded that of amiflamine after a single dose, whereas the N,N-demethylated [FLA 668(+)] was found in low concentrations. The effect on MAO-A correlated significantly with the plasma and the brain concentration of FLA 788(+)[2].

The ex vivo approach was found to be valid for moclobemide in brain and liver and for cimoxatone in brain tissue;?a slight underestimation of the MAO A inhibitory effect of the latter in the liver is likely.?Definite underestimation occurred with amiflamine in both tissues.?Kinetic investigations using homogenates from pretreated rats showed amiflamine to be a competitive inhibitor;?cimoxatone was competitive in the liver but showed a more complex pattern in the brain.?Moclobemide was noncompetitive in both tissues, as has been shown previously for brofaremine.?Moclobemide prevented the deamination of dopamine and serotonin released from their striatal stores by tetrabenazine nearly as efficiently as clorgyline at an otherwise equieffective dose;?cimoxatone was somewhat less effective relative to the reference compound, as was brofaremine, which was however given at a more effective dose.?Amiflamine was much less effective than clorgyline at protecting dopamine, but equieffective with respect to serotonin[1].

DMSO:32.5 mg/mL (169 mM)