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Long-term administration of increasing doses of chlorpromazine (CPZ) in a daily dosage of 10–180 mg produced dyskinetic involuntary movements in the buccolingual area of monkeys. The abnormal movements in the monkeys were associated with an increase in the concentration of dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid in the cerebrospinal fluid (CSF) as well as an increase in the urinary excretion of dopamine, 3-methoxytyramine and noreqinephrine. Short-term administration of CPZ or haloperidol failed to alter either the neurological status or the level of catecholamine metabolities in the CSF and urine of the monkeys. The possible role of an increase in dopamine synthesis in this type of involuntary dyskinetic movement disorder produced by long-term CPZ administration is discussed.

The structural specificity for inhibition of glucose stimulated insulin secretion by indole amines such as serotonin, was studied in an in vitro golden hamster pancreas system. Serotonin is the most potent inhibitor in this series, tryptamine is a weaker inhibitor of insulin release, while 5–methoxytryptamine, melatonin and 5–hydroxyindole acetic acid (S—HIAA) have no inhibitory activity. The inhibition of insulin secretion by serotonin is blocked by some (methysergide maleate) but not blocked by other (cinanserin) serotonin antagonists. It is concluded that in both the indole amine and catecholamine series there is a decrease in inhibitory potency with reduction of the number of hydroxyl groups on the aromatic ring; absence of the aliphatic amine group results in complete loss of inhibitory action.(Endocrinology 91: 809, 1972)

SummaryThe radioprotective effect of 5-methoxytryptamine (Mexamin) was studied on the survival of colony-forming cells. The exogenous method was used in the dose-range 195 to 389 rads, and the endogenous method in the range 486 to 925 rads. The combination of the two methods makes possible reliable determination of the radioprotective effect of Mexamin both in the low and high dose-range. The slope of the curves suggests that the radioprotective effect of Mexamin is not a simple dose-reduction effect.

The N-acetyl group of melatonin was replaced with a histidylphenylalanylarginyl moiety . The product, N-(histidyenylalanylarginy1)-5-methoxytryptamine, reversed the darkening action of α-melanocyte-stimulating hormone (MSH) on frog-skin in vitro in contrast to the closely related tetrapeptide, histidylphenylalanylarginyltryptophan which exhibits intrinsic MSH activity. The synthetic intermediates, N-arginy1-5-meth-oxytryptamine and N-(phenylalanylarginyl)-5-methoxytryptamine also reversed the action of α-MSH. The color lightening potency of these compounds was about one millionth that of melatonin.

Zusammenfassung Methylation of the indole OH of serotonine does not suppress its catatonic action after intracisternal injection in the rat. It appears, on the contrary, that methylation lengthens the time of action of the drug.

The relative potencies of analogues of tryptamine and 5-hydroxytryptamine have been determined on the rat fundus preparation. This tissue had an amine oxidase activity, which, in the homogenate, was able to inactivate both tryptamine and 5-hydroxytryptamine to about the same degree. Amine oxidase inhibitors potentiated the action of tryptamine and many analogues on the isolated rat fundus preparation, but not the action of 5-hydroxytryptamine or of other hydroxytryptamines. This suggested that, in the isolated organ, the amine oxidase was unable to inactivate 5-hydroxytryptamine, but could inactivate tryptamine, 5-methoxytryptamine and many others. These results may be explained if it is supposed that tryptamine entered the cell, but because of the polar hydroxyl group 5-hydroxytryptamine did not. This hypothesis is supported by the oil/water partition coefficients. The structure/activity of the various tryptamine derivatives is discussed in the light of this assumption.

TRYPTAMINE is a normal constituent of human urine1–5; about 30–120 µg of the amine are excreted per 24 h. In blood, tryptamine has hitherto been demonstrated only qualitatively and under pathological conditions in a carcinoid patient6. There is no information about an occurrence of N,N-dimethyltryptamine in human beings. N,N-dimethyl-5-hydroxytryptamine (= Bufotenin) was demonstrated qualitatively as a constituent of normal human urine4,7; in children an excretion of 0–0.03 µg amine/100 mg creatinine has been found with, at most, semi-quantitative methods4. Apparently, N,N-dimethyl-5-hydroxytryptamine was still not demonstrated in blood. 5-Methoxytryptamine has been found in the urine of patients with rheumatic fever8, and that in an order of magnitude of 30–210 µg/24 h.