Excretion of catecholamine metabolites during methadone maintenance and withdrawal.

Catecholamine metabolites excreted by long-term methadone hydrochloride-dependent subjects were studied in a protocol involving a two-study design. After a two-week methadone maintenance period, 15 subjects underwent abrupt methadone withdrawal and 12 subjects, gradual methadone withdrawal. The first study compared levels of catecholamine metabolites excreted during the stable methadone period with those excreted during the abrupt withdrawal period, as well as with those eliminated by healthy nonaddicted controls. No changes in the excretion of 3-methoxy-4-hydroxyphenylglycol and normetanephrine were noted between the methadone maintenance period and the time of abrupt methadone withdrawal. These values did not differ from those obtained for controls. However, higher levels of metanephreine were excreted during the stable methadone period than those in controls. During withdrawal, levels of metanephrine dropped a statistically significant amount in comparison with levels observed during the stable methadone period. The gradual withdrawal study confirmed these findings.

Effect of acute methadone withdrawal on prostaglandin E-stimulated 3H-cyclic adenosine monophosphate accumulation in human platelets.

The effect of acute methadone withdrawal was studied on PGE1-sensitive platelet adenylate cyclase of 8 former heroin addicts who had been stabilized with methadone. During acute methadone withdrawal there was a significant increase in PGE1-sensitive platelet adenylate cyclase activity, which correlated with the severity of withdrawal symptoms. This suggests that PGE1-sensitive adenylate cyclase and cyclic adenosine monophosphate (cyclic AMP) are involved in the human addictive process.

Urinary cyclic AMP excretion by methadone subjects during gradual and acute withdrawal.

Laboratory and animal investigations have supported the hypothesis that levels of cyclic AMP are stable during tolerance to narcotic drugs and increased during withdrawal. In order to test this hypothesis, serial 24-h urinary excretion of cyclic AMP by long-term methadone addicts was determined during a period of stable methadone intake, a period of gradual withdrawal, and a period of acute withdrawal. Cyclic AMP excretion during stable methadone intake is identical to that of normal control subjects. Neither gradual nor acute withdrawal appears to affect the urinary excretion of cyclic AMP. These data agree with previous reports in the literature which suggest that cyclic AMP levels are not altered during tolerance to narcotics, but do not support the hypothesis that levels of the nucleotide might be increased during withdrawal.

Metabolic disposition of 2-phenylethylamine and the role of depression in methadone-dependent and detoxified patients.

We have now postulated that differences in the innate capacity of individuals to synthesize, store and utilize biogenic amines may provide the biological basis for human abuse of narcotic and other drugs, and that these drugs are used in an apparent unconscious effort to self-medicate against an inherent affective disorder. In this communication, we attempted a preliminary characterization of the narcotics withdrawal syndrome on biochemical and clinical parameters. Abstinence was found to be characterized by low urinary excretion of 2-phenylethylamine and depression. An indication for use of tricyclic drugs has been discussed.

DDT-resistance in West African and Asian strains of Aedes aegypti (L.).

The yellow fever mosquito Aedes aegypti has developed resistance to DDT in the Caribbean region and in South-East Asia, but not in West Africa. Therefore West African strains were compared with South-East Asian strains for their response to laboratory selection with DDT. It was found that West African strains were much slower to respond initially, but eventually could build up a high degree of DDT-resistance. By crossing and backcrossing with a susceptible marker-gene strain, it was found that this resistance was due to a single gene linked with the gene y (yellow) on chromosome 2 at a cross-over distance of approximately 35 units in an Upper Volta strain as in a Bangkok strain; interstrain crosses indicated that the gene was the same as that in a Trinidad strain and in one from Penang. Dieldrin-resistance could be readily induced in the Upper Volta strain and proved to be due to a gene also linked with y but at a crossover distance of approximately 25 units, comparable to that in Caribbean strains previously studied. Material from Karachi, West Pakistan, developed a dieldrin-resistance also showing 25% crossing over with y, and a DDT-resistance also linked with this chromosome-2 marker gene.