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Mazindol, 5-hydroxy-5-(4'-chlorophenyl)-i, 3-dihydro-5H-imidazo-(2, 1-a) isoindole, has demonstrated anorexic activity and other pharmacological responses which suggest alterations in brain norepinephrine metabolism. Studies of the effects of mazindol on neuronal uptake and/or release of norepinephrine showed that mazindol, when given before cerebral intraventricular injection of 3-H-norepinephrine by a mechanism that increases 3-H-normetanephrine synthesis via catechol-O-methyl-transferase and provided no significant effect on deamination of the catecholamine. Studies designed to measure norepinephrine release showed that mazindol (in contrast to d-amphetamine) did not cause release of 3-H-norepinephrine from neuronal stores. Furthermore, mazindol did not inhibit norepinephrine synthesis, whereas d-amphetamine did. The effect of d-amphetamine on norepinephrine release and synthesis may be more important than effects on uptake of this catecholamine. In contrast, mazindol appears to produce its primary effect on norepinephrine metabolism by inhibition of neuronal uptake mechanism.

The sensitivity to isoprenaline of beta inhibitory adrenoceptors of tracheal chain preparations from guinea-pig, rabbit and rat was compared. For this purpose the tracheal chain preparations were contracted either with KCl or pilocarpine. Isoprenaline (1.0 X 10(-7)M--6.4 X 10(-6)M) caused concentration-related relaxation of guinea-pig trachea, whereas the rabbit and the rat trachea remained insensitive even at very high concentrations of isoprenaline (2.5 X 10(-3)M). Phenoxybenzamine (2.6 X 10(-6)M) potentiated or unmasked the relaxant effects of isoprenaline respectively in the guinea-pig or the rabbit and the rat trachea contracted with KCl. Phentolamine was ineffective in potentiating or unmasking the relaxant effects of isoprenaline. The potentiating or unmasking effects of phenoxybenzamine were absent in reserpinized preparations and lidocaine treated preparations from both guinea-pig and rat. Normetanephrine (5.4 X 10(-7)M) potentiated responses to isoprenaline only in the guinea-pig trachea. Even a 10-fold higher concentration of normetanephrine was ineffective in the rabbit or the rat rachea.

The concentrations 5-hydroxytryptamine, noradrenaline, their precursors and metabolites have been determined in three regions of mouse brain following gonadectomy; the rates of depletion of 5-hydroxytryptamine and noradrenaline following synthesis blockade have also been examined. Previous investigations have shown that gonadectomy results in changes in hypothalamic catecholamine metabolism; this report shows that changes are not confined to the hypothalamic area and suggests that the effects in other areas of the brain may contribute to the increased incidence of mental disturbances in man when hormone levels are drastically altered. Gonadectomy results in reduced 5-hydroxytryptamine and 5-hydroxyindoleacetic acid concentrations in all regions of the mouse brain. Normetanephrine concentrations are significantly increased and the rate of depletion of noradrenaline from the brain following synthesis blockade is markedly accelerated following gonadectomy; this suggests that circulating steroid sex hormones may exert a stabilising effect on brain catecholamine stores.