Biomedical subjects
D X Freedman
Publications and source records attributed to D X Freedman.
Neurotransmitter abnormalities in patients with motor neuron disease.
In 22 patients with motor neuron disease (MND), the mean concentration of serotonin (5HT) in platelets was slightly increased, platelet monoamine oxidase (MAO) activity was significantly increased, and plasma concentrations of total and both free and bound tryptophan were significantly decreased. Though platelet MAO activity was positively correlated with concentrations of 5HT, independent causal mechanisms are probable. When patients were rated according to severity, highest values of platelet 5HT and MAO activity were found in the most severely affected group, whereas concentrations of both total and protein-bound tryptophan were most decreased. Changes in concentrations of 5HT and tryptophan may reflect compensatory changes in response to degeneration of motor neurons or to interruption of their monoaminergic innervation.
Blood tryptophan metabolism in chronic schizophrenics.
Concomitant measures of blood indole metabolism were conducted in 33 chronic schizophrenics who showed significantly elevated mean platelet serotonin (5-HT) values and lower platelet monoamine oxidase (MAO) and plasma amine oxidase activities than normals. When subdivided according to Research Diagnostic Criteria diagnosis, the 20 chronic undifferentiated (CU) schizophrenics showed these same deviations from normal; the 13 chronic paranoid (CP) schizophrenics also had significantly higher mean 5-HT values but significantly lower plasma concentrations of total and bound tryptophan. In CP schizophrenics, platelet MAO activity, but not plasma amine oxidase activity, was significantly lower than in CU schizophrenics and controls. Hyperserotonemia occurred in 11 of the chronic patients (33%); nine were CU schizophrenics. In the latter, total tryptophan concentration was significantly lowered. Hyperserotonemia was not associated with reduced liver tryptophan pyrrolase activity or platelet MAO or plasma amine oxidase activities; rather, it may be a consequence of enhanced tissue tryptophan uptake and utilization.
Response to the presidential address.
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Tryptophan metabolism in children with attentional deficit disorder.
The authors present the first report, to their knowledge, of hyperserotonemia in children with attentional deficit disorder who had normal intelligence. Hyperserotonemic children had significantly lower levels of plasma total and protein-bound tryptophan and a higher percentage of free tryptophan than those with normal serotonin levels. Plasma kynurenine did not differ, suggesting that the hyperserotonemia is not due to a blockade of the kynurenine pathway but may reflect on increase in tissue tryptophan uptake and use.
Blood monoamine metabolism in Huntington's disease.
In 25 patients with Huntington's disease (HD), the mean blood concentration of serotonin (5-HT) and percentage of plasma free tryptophan were significantly increased while plasma concentrations of total and protein-bound tryptophan were significantly decreased. The pattern of changes in tryptophan concentrations was related to clinical severity but not to 5-HT levels. Platelet monoamine oxidase (MAO) activity was significantly increased in patients with HD; kinetic and marker enzyme studies suggested an increased enzyme concentration. Offspring at risk for HD also had elevated platelet MAO activity but normal concentrations of blood 5-HT and plasma tryptophan. In ten patients, plasma epinephrine concentrations were significantly increased; plasma dopamine and norepinephrine concentrations were positively related to MAO activity. The finding of peripheral neurotransmitter abnormalities in HD raises the question of an interaction between CNS and peripheral processes or a systemic disorder of neurotransmitter metabolism.
Will the real doctor please stand up?
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The President's Commission: realistic remedies for neglect. Pragmatic next steps--not a trip.
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Rat brain aryl acylamidase: multiple forms and inhibition effects of LSD, serotonin and related compounds.
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Hyperserotonemia and amine metabolites in autistic and retarded children.
Mean whole blood serotonin (5-HT) levels were elevated in groups of autistic and severely retarded children. Eight of 27 (30%) individual autistic children, 13 of 25 (52%) severely retarded children, two of 23 (9%) mildly retarded children, and none of the control children had statistically significant blood 5-HT levels elevations (hyperserotonemia). Hyperserotonemic autistic children excreted more urinary 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), tryptamine, and vanillylmandelic acid than did mildly retarded children with normal blood 5-HT levels. Rates of depletion and repletion of blood 5-HT levels in these two groups following reserpine therapy were identical. Oral tryptophan administration doubled urinary 5-HIAA excretion in both groups and raised urinary 5-HT levels in hyperserotonemic autistic children, but lowered urinary 5-HT in mildly retarded, normal blood 5-HT children. No clear mechanism for hyperserotonemia was found; the rationale for further investigations is discussed.
Vesicular and juxtavesicular serotonin: effects of lysergic acid diethylamide and reserpine.
An extensive analysis of subcellular serotonin (5-HT) compartmentation with and without reserpine was undertaken in order to localize further the effect of LSD on rat brain 5-HT. Modification of the subfractionation procedure resulted in an increase in purity of fractions and a decrease in variability of 5-HT content. With the modified procedure, the administration of LSD produced a significant increase in 5-HT in the nerve-ending fraction prepared from rat whole brain. LSD caused a 50% increase in 5-HT in the vesicular fraction which was recovered after osmotic disruption of nerve-endings. The increase of 5-HT in the vesicular fraction after LSD was not demonstrable in rats treated with reserpine for as long as 2 weeks postreserpine. Instead, with reserpine pretreatment the LSD-induced increase in 5-HT was localized to the intrasynaptosomally derived "end supernatant" as early as 48 hours postreserpine. Thus, an unanticipated "juxtavesicular" site capable of 5-HT retention or binding was detected. In crude subcellular fractions, by contrast, significant increase in 5-HT were not observed with LSD administration until 4 days after reserpine, at which time at least a 50% 5-HT repletion had occurred. This study of drug interactions suggests a juxtavesicular compartment that may be of functional importance in presynaptic binding or transport of 5-HT.
Editorial: The alma mater is smoking--this is dangerous to your health! Payoff and payback.
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Cardiovascular and subjective effects of intravenous cocaine administration in humans.
Nine volunteer subjects were tested with intravenously administered cocaine hydrochloride in doses ranging from 4 to 32 mg, as well as 10 mg of dextroamphetamine sulfate. Measures of cardiovascular and subjective effects were made. Generally parallel dose-effect functions were obtained for heart rate, blood pressure, Addiction Research Center Inventory scores, Profile of Mood Scales, and subject ratings. A substantial effect on each of these variables was recorded after 8 mg of cocaine. The increase continued and peaked at approximately 16 mg after which it usually leveled off. Ten milligrams of dextroamphetamine generally had an effect comparable to 8 to 16 mg of cocaine.
Rat brain aryl acylamidase: stereospecific inhibition by LSD and serotonin-related compounds.
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Stereospecific receptor sites for d-lysergic acid diethylamide in rat brain: effects of neurotransmitters, amine antagonists, and other psychotropic drugs.
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