Monoamine oxidase inhibitors distribution

Monoamine oxidase inhibitors are rapidly and completely absorbed orally reaching peak blood levels within 2 h. Monoamine oxidase inhibitors are acety-lated in the liver to many active and inactive metabolites. The volume of distribution is estimated to range from 1 to 41 kg The inactive metabolites are excreted by the kidneys. The elimination half-lives of monoamine oxidase inhibitor parent compounds range from 15 min to 3.5 h. The biologic half-life often significantly exceeds the elimination half-life. 

Itzhak, Y., Stein, I., Zhang, S.H., Kassim, C.O., Cristante, D., 1991. Binding of sigma-ligands to C57BL/6 mouse brain membranes effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of sigma-receptor subtypes. J. Pharmacol. Exp. Ther. 257, 141-148. 

An explanation of the mode of action of the monoamine oxidase inhibitors in terms of their intervention in central transmission processes is difficult for several reasons. Monoamine oxidase is widely distributed in the body and some of the consequences of its inhibition may arise peripherally in the brain the enzyme participates in the inactivation of at least three substances (noradrenaline, dopamine and 5-hydroxytryptamine). Not all monoamine oxidase inhibitors have antidepressant activity but those that have may owe at least part of their activity to an action other than enzyme inhibition. 

PscHEiDT, G. R. and Himwich, H. E., Reserpine, monoamine oxidase inhibitors, and distribution of biogenic amines in monkey brain, Biochem, Pharmacol 12, 65 (1963). 

Monoamine Oxidases and their Inhibitors. Table 3 Distribution and proportions of the A and B forms of monoamine oxidases in adult rat and human tissues... 

Monoamine oxidase (MAO) is an enzyme present in the outer mitochondrial membrane of neuronal and non-neuronal cells. Two isoforms of MAO exist MAO-A and MAO-B. The MAO enzymes are responsible for the oxidative deamination of endogenous and xenobiotic amines, and have different substrate preferences, inhibitor specificities, and tissue distributions. MAO inhibition allows endogenous and exogenous substrates to accumulate, and may thereby alter the dynamics of regular monoamine transmitters, such as norepinephrine, serotonin, and dopamine. Specifically, MAO-A deaminates serotonin, norepinephrine, and dopamine, and MAO-B deaminates dopamine, [3-phenylethylamine, and benzylamine. In the human brain, about 75% of MAO is of the B subtype. Hence, the primary effect of MAO inhibitors (MAOIs) is to increase the availability of these neurotransmitters at the nerve terminal. 

Monoamine oxidase plays a critical role in the regulation of monoamine neurotransmitters such as serotonin, noradrenaline, and dopamine. MAO isoenzymes are classified on the basis of their substrate preference, sensitivity toward spiecific inhibitors, and tissue distribution into MAO-A and MAO-B. Selective MAO-A inhibitors have been used clinically in the treatment of depression and anxiety, while MAO-B inhibitors have been used in the treatment of Parkinson s and Alzheimer s diseases. Many plant-derived and synthetic compoxmds such as isoquinolines and xanthones have been identified as MAO inhibitors. In (Deeb and dare, 2008b) the monoamine oxidase (MAO)-inhibitory activity of 46 phenylisopropylamines expressed as pICSO is modeled with the orientations of nodes in n -like orbitals of the phenyl ring and some other descriptors using flip regression analysis. The... 

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