Catecholamine metabolism during heroin use.

The authors examined urinary levels of catecholamines and metabolites during a 10-day period of heroin use in 9 subjects. Catecholamine and metabolite excretion increased over baseline values on the first day of heroin use, but markedly different patterns of change emerged later. In contrast to the significant increase in normetanephrine and decrease in metanephrine excretion in all 9 subjects during heroin use, only 4 subjects showed an increase in 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion. Moreover, it appeared that the increase in MHPG excretion in this subgroup began on the day before heroin administration, which suggests the possibility of an anticipatory or conditioned response.

The effects of tranylcypromine isomers on norepinephrine-H3 metabolism in rat brain.

The effects of d- and l-tranylcypromine on the disposition and metabolism of intracisternally administered l-norepinephrine-H3 were studied in rat brain. Both isomers inhibited the deamination of norepinephrine-H3. However, d-tranylcypromine was considerably more potent than the l-isomer in this respect. In addition, the l-isomer of tranylcypromine was found to enhance the disappearance of endogenous and tritiated norepinephrine from brain. Although this action appeared to result from an increase in catecholamine release, the possibility of uptake inhibition could not be eliminated. The l-isomer of tranylcypromine enhanced the disappearance of norepinephrine-H3 from brain when administered both 20 and 90 min following intracisternal injection of the label. Comparable doses of d-tranylcypromine did not exhibit this effect. Larger increases in brain levels of normetanephrine-H3 were produced by d,l-tranylcypromine than by either the d- or l-isomer alone, indicating that the racemic mixture may produce the greatest increase in the interaction of norepinephrine with its postsynaptic receptors.

Opiates, catecholamines, behavior, and mood.

Indirect evidence has linked opioid reinforcement with changes in noradrenergic metabolism secondary to drug administration. Methodological precedents for biobehavioral correlations in depressive illness have suggested an important association between changes in mood and biogenic amine excretion patterns in the urines of patients during depression and recovery. This paper presents preliminary data on the possible relationship between changes in catecholamine excretion that were observed and the changes in behavior, mood, psychiatric status, and cardiorespiratory physiology secondary to heroin administration and methadone-assisted withdrawal. This study focuses on the urinary excretion of MHPG, since an appreciable fraction of this metabolite is probably derived from norepinephrine originating in the brain. The subjective changes in mood associated with heroin use, the decrease in respiratory rate, and the behavioral and mental status effects associated with opiate intoxication were observed only in the individuals whose MHPG excretion increased during the period of opiate administration.

The effects of heroin on catecholamine metabolism in man.

In a study of the effects of heroin administration in nine human subjects, urinary catecholamines and metabolites were examined during an initial drug-free baseline period, a ten-day period of heroin administration and a subsequent period of methadone detoxification. All catecholamines and metabolites tended to be increased over baseline values on the first day of heroin administration. However, markedly different patterns of change emerged on subsequent days of heroin administration. Norepinephrine and normetanephrine remained increased throughout heroin administration. Epinephrine was increased during the early phase of heroin administration but returned to baseline values during the latter phase of heroin administration. After the increase on the first day of heroin administration, metanephrine decreased and substantial decrements below baseline values occurred during the latter phase of heroin administration. After increasing on the first day of heroin administration, 3-methoxy-4-hydroxy-mandelic acid (VMA) returned to approximately baseline values. During heroin administration, an increase in 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was observed in a subgroup of four of the nine subjects studied. This is in contrast to the increase in normetanephrine excretion and the decrease in metanephrine excretion that was observed in the entire group of nine subjects. It is conceivable that persistance of, or development of, tolerance might account for the failure to observe an increase in MHPG excretion in all of the subjects. It appeared as if the increase in MHPG excretion began on the day prior to the administration of heroin in the subgroup of patients with increased MHPG excretion during heroin administration, suggesting the possibility of an anticipatory or conditioned response, with the anticipation of heroin producing an increase in MHPG excretion.