Melatonin has blocked adventitious movements induced by L-dopa in intact mice. It has reversed the adventitious turning to the right, and it has induced running to the left in mice receiving L-dopa after a lesion in the right caudate nucleus.

Transportation of manganese, L-dopa, and L-tryptophan was slower through the tissues, of intact pallid mice than through those of black C57Bl/6J mice, presumably because of the influence of the gene pallid.

We determined the concentrations of manganese in whole blood and hair in 52 epileptics, 6 blood relatives, and 24 normal controls. Blood, and possibly hair manganese content, was significantly lower in treated epileptics than in controls (p less than 0.002). Although not all patients showed reduced tissue manganese levels, most of those with frequent seizures had manganese levels falling below the lowest control level, suggesting a relationship between manganese tissue levels and high seizure activity. These differences in manganese levels were not correlated with the type, dose, or plasma levels of anticonvulsant medication. Reduced manganese availability at the neuronal level, where Mn++ stabilizes membrane excitability, may affect epileptogenic lesions to increase the likelihood of seizure activity.

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1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, c-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes 6-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment. IntroductionIt has long been recognized that haem synthesis in man is severely affected by increased body lead burden. This inhibition of haem production is well known to result in decreased levels of circulating haemoglobin in lead-exposed individuals. The possibility of altered drug metabolism due to inhibition of synthesis of the microsomal haemoprotein cytochrome P-450 has been the subject of a number of studies both in man and animals.Recent reports (Alvares, Kapelner, Sassa & Kappas, 1975; Meredith, Campbell, Moore & Goldberg, 1977)

Various concentrations of L-dopa (levodopa, L-3,4-dihydroxyphenylalanine) were incorporated in the diets of young male Swisg albino mice, and the highest coneentrations to which these mice became adapted within 3 weeks were determined. One such concentration administered indefinitely eventually indticed a youthful appearance, a signifilantly prolonged life-span, but also corneal opaeities compatible with traumatic or chemical keratitis.The use of idopa (L-3,4-dihydroxyphenylalanine, levodopa) in the long-term treatment of Parkinson's disease, a chronic affliction, necessitates initial adaptation to high doses followed by sustained consumption of this amino acid (1, 2). Like other long-term regimens, treatment with t-dopa requires the physician's skill and care and the patient's cooperation, and even so, certain side effects can emerge (3). Shortly after the publication of papers describing the therapeutic effects of L-dopa (1, 2), many kinds of illness in patients with Parkinsonism wete being ascribed by others to idopa as its side effects, whether or not the recommended regimen was followed. The accruing literature, too voluminous even for references here, gave rise to fears about the long-term influence of idopa on patients' general health. These fears have been slow to recede despite (i) subsequent reports that iLdopa is the most effective drug for treating Parkinson's disease (see ref. 4) and (ii) the fact that no deaths of treated patients have been ascribed to idopa, in sharp contrast to findings with all other major drugs.In our investigations on the effects of L dopa on general health, we initiated animal experiments to supplement our long-term observations on human patients. Since life-span can be considered as an indicator of health, we determined the maximal concentrations of -dopa incorporated in the chow to which mice could become adapted so that we could then study the effects of a very high concentration on longevity. The results show that this amino acid could either kill the mice or significantly extend their life-span and apparent prime of life, depending on the way it was given. Some of the longevity data, although preliminary, are being presented here to expedite studies of the relevance of these long-lasting experiments to human patients. MATERIALS AND METHODSAnimals. Most of the animals were 4-5 week-old, male Swiss albino mice of the Hale-Stoner strain. In some experiments females of the same strain and age, and aging males, were also used. Cages containing six mice (or two, in the case of aging males) were kept in air-conditioned rooms with controlled humidity, lighted 12 hr each day.Diets. Ground Purina chow was given freely, plain for the controls and with certain concentrations of idopa (levodopa, i-3,4-dihydroxyphenylalanine, Nutritional Biochem. Corp.) added for the test mice. The Purina chow itself, in contrast to some other rodent diets (5, 6), did not contain a measurable amount of idopa. The different -dopa concentrations in the chow mixtures, as determined spectrofl...