Investigation of dopamine (DA) metabolism in humans is useful in order to get a deeper knowledge of neuropsychiatric disorders involving an altered DA transmission. The first reaction of the DA oxidative pathway, consists in oxidative deamination, carried out by monoamine oxidase (MAO). The direct product of MAO activity is dihydroxyphenylacetaldehyde (DOPALD), which is immediately converted into dihydroxyphenylacetic acid (DOPAC). It is known that pharmacological inhibition of MAO, in animals as well as in humans, produces wide neurophysiological effects by modulating neurotrasmitter function. The activity of MAO can be evaluated by using several approaches, like: specific MAO inhibitors; radiotracers to examine the metabolic fate of catecholamines (CAs) and their metabolites; or, finally, deriving metabolic data from subjects with a genetically determined absence of one or both MAO isofonns (called MAO-A and MAO-B). Unfortunately, owing to the rapid conversion of DOPALD to DOPAC, the detection of the direct product of MAO (DOPALD), in vivo, has revealed a very difficult step to measure MAO activity. More recently, trans-striatal dialysis studies, performed in rats, in combination with either GLC mass-spectrometry or HPLC system and coulometric electrochemical analysis, have made possible to detect the aldehyde present in the extracellular fluid. Such a new experimental procedure, joined with the availability of mice selectively knocked out for the isoenzymes MAO-A or MAO-B
Recent advances in dopamine metabolism in relation to neuropsychiatric disorders
FERRUCCI, MICHELA;GESI, MARCO;GIORGI F;FORNAI, FRANCESCO
2000-01-01
Abstract
Investigation of dopamine (DA) metabolism in humans is useful in order to get a deeper knowledge of neuropsychiatric disorders involving an altered DA transmission. The first reaction of the DA oxidative pathway, consists in oxidative deamination, carried out by monoamine oxidase (MAO). The direct product of MAO activity is dihydroxyphenylacetaldehyde (DOPALD), which is immediately converted into dihydroxyphenylacetic acid (DOPAC). It is known that pharmacological inhibition of MAO, in animals as well as in humans, produces wide neurophysiological effects by modulating neurotrasmitter function. The activity of MAO can be evaluated by using several approaches, like: specific MAO inhibitors; radiotracers to examine the metabolic fate of catecholamines (CAs) and their metabolites; or, finally, deriving metabolic data from subjects with a genetically determined absence of one or both MAO isofonns (called MAO-A and MAO-B). Unfortunately, owing to the rapid conversion of DOPALD to DOPAC, the detection of the direct product of MAO (DOPALD), in vivo, has revealed a very difficult step to measure MAO activity. More recently, trans-striatal dialysis studies, performed in rats, in combination with either GLC mass-spectrometry or HPLC system and coulometric electrochemical analysis, have made possible to detect the aldehyde present in the extracellular fluid. Such a new experimental procedure, joined with the availability of mice selectively knocked out for the isoenzymes MAO-A or MAO-BI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
