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The present study has examined whether MAO-B has a role in DA metabolism in the primate CNS in situ. Eleven macaques (macaca facicularis) were used in this study to examine the effects of (-)-deprenyl (1 mg/kg, i.v., 2 and 24 hours). (-)-Deprenyl administration completely and selectively blocked MAO-B activity and blocked DA metabolism in the caudate nucleus and frontal cortex. DA metabolism in the substantia nigra was not affected by MAO-B inhibition. Changes in DA metabolism were accompanied by changes in 5-hydroxytryptamine (5HT) turnover: 5-hydroxyindole acetic acid (5HIAA) levels increased in the caudate and decreased in the frontal cortex. Levels of 2-phenylethylamine (PE), a putative modulator of dopaminergic transmission, were increased by MAO-B inhibition in all three brain regions examined. It is concluded that in some regions of the primate brain, in contrast to the rat, MAO-B has an important role in DA metabolism.

Behavioral and pharmacological effects of oral administration of L-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected by L-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested that L-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects of L-deprenyl on behavior and cognitive function.

Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), beta phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.

Using a new ultrasensitive method the trace biogenic amines, phenylethylamine, meta-tyramine and para-tyramine have been quantitated in brain regions obtained from a single rat. Phenylethylamine concentrations in ng/g wet tissue (mean +/- std. error) were as follows: caudate 2.71 +/- 0.73, hypothalamus 0.45 +/- 0.15, cerebellum 0.09 +/- 0.02, olfactory bulb 0.35 +/- 0.11, stem 0.13 +/- 0.03, hippocampus 0.20 +/- 0.11, cortex 0.69 +/- 0.13 and the rest (remainder of the brain) 2.81 +/- 0.41. Mean whole brain was 1.23 +/- 0.19 ng/g, in agreement with previous measurements. meta-Tyramine concentrations (ng/g) were: caudate 2.69 +/- 0.19, hypothalamus 0.32 +/- 0.16, cerebellum 0.07 +/- 0.04, olfactory bulb 0.09 +/- 0.04, stem 0.04 +/- 0.01, hippocampus 0.07 +/- 0.02, cortex 0.18 +/- 0.15 and the rest 0.15 +/- 0.06, with a mean whole brain value of 0.26 +/- 0.05 ng/g and para-tyramine concentrations were: caudate 8.99 +/- 1.60, hypothalamus 0.93 +/- 0.13, cerebellum 0.78 +/- 0.27, olfactory bulb 0.70 +/- 0.13, stem 0.90 +/- 0.36, hippocampus 0.40 +/- 0.06, cortex 1.78 +/- 0.28 and the rest 2.38 +/- 0.12 and mean whole brain was 1.90 +/- 0.25 ng/g. In human plasma the concentrations of the three amines were found to be 31.3 +/- 3.4 pg/ml, 5.3 +/- 1.6 pg/ml and 66.0 +/- 9.9 pg/ml respectively and in dog blood 95.3 +/- 4.6 pg/ml, 24.0 +/- 7.6 pg/ml and 486 +/- 43 pg/ml respectively. When monoamine oxidase inhibitors were added to the blood immediately after collection there were no significant increases in the amine levels indicating that MAO-B is not present in plasma in significant quantities.

Through use of the high-resolution double-focusing mass spectrometer, copper has been identified in various regions of the mouse, rat, guinea pig, rabbit, and human brain. The procedure depends on converting the copper (in ashed tissue) to its chloride salt, followed by derivatization with tetraphenylporphyrin (TPP) to yield a TPP chelate. After chromatographic separation, this chelate is assessed in the mass spectrometer by the integrated-ion-current procedure. Deuterated metal TPP chelates and the rare stable isotope(65)Cu were used as internal standards. Whole brain values obtained were as follows: mouse, 6.67±0.16 (mean±SEM) μg/g wet weight of tissue; rat, 1.06±0.05; guinea pig, 5.40±0.63; and rabbit, 7.52±0.76. In the rat, the cerebellum contained the highest concentration (1.25 μg/g), and the striatum the lowest (0.70 μg/g). In the human brain, the cortex (gray) and the striatum were relatively the highest copper-containing regions, with the cerebellum (white) being the lowest.