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[Enzymatic N-acetylation of tryptamine by brain homogenates of Locusta migratoria before and after intoxication by chlordimeform or lindane (author's transl)].

Brain homogenates of Locusta migratoria are found to possess enzyme capable of catalyzing the N-acetylation of tryptamine. A main product of the enzymatic reaction is isolated and identified as N-acetyltryptamine by chromatography analyse. Both insecticides, chlordimeform and lindane, inhibit enzyme activity. A direct correlation between the degree of intoxication and acetylation of tryptamine is described.

Acetylation

Effects of tranylcypromine and pargyline on brain tryptamine.

Tranylcypromine produces behavioral excitation while pargyline produces depression. Tranylcypromine increased brain tryptophan which led to an accumulation of tryptamine. The levels of tryptamine after tranylcypromine were found to be 3 times those found after pargyline.

Animals

Purification and properties of strictosidine synthetase (an enzyme condensing tryptamine and secologanin) from Catharanthus roseus cultured cells.

Strictosidine synthetase, which catalyzes the condensation of tryptamine with secologanin to form strictosidine (isovincoside), was purified 740-fold to homogeneity from cultured cells of Catharanthus roseus in 10% yield. The specific activity is 5.85 nkat/mg. The molecular weight as estimated by gel filtration is 38,000. The isoelectric point is 4.6. Apparent Km values for tryptamine and secologanin are 0.83 and 0.46 mM, respectively. The enzyme shows a broad pH optimum between 5.0 and 7.5. The product of the enzymic reaction is exclusively strictosidine, while no trace of its epimer vincoside can be detected. Sulfhydryl inhibitors have no effect on the enzyme. End products in the biosynthetic pathway of indole alkaloids such as ajmalicine, vindoline, and catharanthine do not inhibit the activity of strictosidine synthetase.

Carbon-Nitrogen Lyases

In vitro half-life of 14-C-tryptamine in whole blood of drug-free chronic schizophrenic patients.

The authors found higher in vitro 14C-tryptamine half-lives in the blood of 10 drug-free chronic schizophrenic patients than in the blood of 13 mentally normal control subjects. This finding was negatively correlated for both groups with platelet MAO activity. Repeated determinations of in vitro 14C-tryptamine half-lives over a period of 5 months were positively correlated for the patients, although some blood samples showed statistically significant variability.

Adult

Interaction of drugs with apomorphine, tryptamine and norepinephrine. A new 'in vivo' approach: the ATN-test in rats.

A new experimental test procedure is described for the 'in vivo' study of drug interactions with dopamine (DA), 5 hydroxy-tryptamine (5-HT) and norepinephrine (NE). The ultimate aim of this study is to provide an empirical evaluation of the relative specificity with which drugs may affect particular neurotransmitter systems, and to allow a classification of new drugs in this respect. The data indicate that, within certain dosage limits, compounds may modulate specifically a single component of the test procedure and may thus be considered as interacting specifically to modify one neurotransmitter system: i.e. DA in the apomorphine-test (e.g. pimozide), 5-HT in the tryptamine-test (e.g. pizotifen) and NE in the norepinephrine-test (e.g. phenoxy-benzamine). Higher doses of the same compounds may, however, excert effects on other neurotransmitter systems as well, and these actions may be classified as nonspecific. Thus the concept of drug specificity as applied in the present study, is not exclusive, but refers to the dissociation, in terms of doses, which exists between a drug's effect on one neurotransmitter system and its possible effects on other systems. The ATN-test separates and delineates, in terms of doses, the specific and nonspecific effects of drugs.

Animals

Modification of the effects of LSD-25, d-amphetamine and tryptamine on electrically evoked responses in the visual system by methiothepin and octoclothepin.

LSD-25 (32 microgram/kg), d-amphetamine (3.2 mg/kg), and tryptamine (320 to 3200 microgram/kg) given intravenously depressed the response recorded in the visual cortex to electrical stimulation of the optic chiasm of the chloralose anesthetized cat. Relatively large doses of 1 mg/kg of the dibenzothiepin derivatives, methiothepin and octoclothepin, antagonized the depressant effects of both LSD-25 and tryptamine to a greater degree than d-amphetamine.

Animals

Evidence for the presence of m-tyramine, p-tyramine, tryptamine, and phenylethylamine in the rat brain and several areas of the human brain.

Postmortem human brains have been obtained from four nonpsychiatric patients, aged 59-70 years. Regional analysis of the trace amines phenylethylamine, p-tyramine, m-tyramine, and tryptamine has indicated that the amines are distributed heterogeneously throughout the brain, but are most concentrated in the basal ganglia. Although the levels are very low, evidence obtained from animal studies has indicated that the trace amines have a very rapid turnover rate. Their presence in a brain synaptosomal fraction suggests a possible involvement in the process of neurotransmission. Postmortem changes in human brain amines are discussed in relation to those occurring postmortem in the rat brain, in which phenylethylamine, p-tyramine, and tryptamine have been shown to increase to levels greater than those prevailing in vivo.

Aged

Mass spectra of some specifically deuterated tryptamines.

The mass spectra of the four tryptamine derivatives, N-acetyl-5-methoxytryptamine (melatonin), N-acetyl-5-hydroxytryptamine (N-acetyl-serotonin), N,N-dimethyl-5-hydroxtryptamine (bufotenine) and N,N-dimethyl-5-methoxytryptamine (O-methylbufotenine), with specifically labeled [D4] aminoethyl sidechains have been measured. Comparison of these spectra with those of the unlabeled compounds enable the major fragmentations of the compounds to be defined.

Bufotenin

Quantitative assay of the N-methylated metabolites of tryptamine and serotonin by gas chromatography mass spectrometry as applied to the determination of lung indoleethylamine N-methyltransferase activity.

A specific and sensitive method is described for the identifcation and quantification of the N-mono- and dimethylated derivatives of tryptamine and serotonin by gas chromatography mass spectrometry. Deuterated analogues of the amines have been prepared for use as internal standards. The technique has been applied to the determination of indoleethylamine N-methyltransferase activity in rabbit and human lung. No interference from the beta-carboline formation or other side reactions between the substrates and the methyl donor was observed.

Animals

The detection, identification and measurement of indole, tryptamine and 2-phenethylamine in putrefying human tissue.

Indole, tryptamine and 2-phenethylamine are putrefactive products which may be found in decaying human tissue. They may be identified by the data given found in decaying human tissue. They may be identified by the data given for infrared and ultraviolet spectrometry, fluorometry, thin layer and gas chromatography and mass spectrometry. Quantitative studies may be made using the gas chromatography method described. The rate of formation is affected by temperature and preservatives and may be prevented if necessary by the use of sodium fluoride. No relationship between the production of these materials (and alcohol) and time since the post-mortem examination could be established. The post-mortem examinations took place within 24 hours of death.

Ethanol

Serotonin receptor binding affinities of tryptamine analogues.

Using a rat fundus model, the serotonin (5-HT) receptor binding affinities of 27 tryptamine analogues were determined. Factors which might affect affinity were examined, e.g., lipids solubility, as reflected by partition coefficient, and pKa. Structure-activity relationships were developed and are discussed in terms of substituents on the terminal amine, the side chain, and the indole 1 position, the 5 position, and at other positions on the indolic nucleus. If lipid solubility and metabolism can be accounted for, there appears to be a parallelism between 5-HT receptor binding affinities and the hallucinogenic (psychotomimetic) potencies of several of these compounds.

Animals

5-Hydroxytryptamine and tryptamine pathways in scleroderma.

Levels of 5-hydroxyindoleacetic acid, indoleacetic acid and total indoles were determined in the urine of 23 patients with systemic scleroderma and 7 patients with cutaneous scleroderma, before and after peroral loading with L-tryptophan (0-1 g/kg body weight). Before loading, 5-hydroxyindoleacetic acid levels were normal in nearly all cases of systemic scleroderma as well as of cutaneous scleroderma; however after loading, in nearly one half of cases there was no normal increase of this metabolite. These results suggest impaired transformation of serotonin into 5-hydroxyindoleacetic acid. A disproportionately high ratio of total indoles to indoleacetic acid suggests the presence of excess of tryptamine. The results of the study may indicate that in scleroderma metabolism of biogenic amines derived from tryptophan is abnormal, probably as a result of impaired activity of monoamine oxidase.

Adolescent

Effects of monoamine oxidase inhibitors on the borohydride stabilizable binding of serotonin and tryptamine in brain.

The in vivo and in vitro effects of various monoamine oxidase inhibitors (MAOI) on the borohydride stabilizable finding of serotonin (5-HT) or tryptamine in brain was investigated. A significant correlation between the extent of Mao inhibition and the amount of stabilized binding of the indolealkylamines was demonstrated. All hydrazine-type MAOI and harmine, a reversible nonhydrazine-type MAOI, employed in vitro, were shown to decrease the binding. beta-Phenylisopropylhydrazine apparently blocks the receptor carbonyl groups in the brain in vitro as well as in vivo.

Animals

Dual mechanism of the stimulant action of N,N-dimethyl-5-hydroxy-tryptamine (bufotenine) on cardiac sympathetic nerves.

The indirect sympathomimetic effects of N,N-dimethyl-5-hydroxytryptamine (bufotenine) have been analysed on the rabbit heart perfused in vitro by the Langendorff technique. Comparisons have been made with the effects of 5-hydroxytryptamine (5-HT), which activates tryptamine receptors, and dimethylphenylpiperazinium (DMPP), which stimulates nicotine receptors. Bufotenine, 5-HT and DMPP stimulated the rate and force of cardiac contraction but whereas all were powerful stimulants of cardiac rate, bufotenine and DMPP were much stronger stimulants of atrial and particularly ventricular tension than 5-HT. Responses to 5-HT were markedly reduced by perfusion of hearts with an excess of 5-HT, and those to DMPP, during perfusion with hexamethonium. A combination of 5-HT with hexamethonium was necessary to abolish the effects of bufotenine. The data suggest a dual mechanism of stimulant action of bufotenine on the cardiac sympathetic nerves of the rabbit heart involving activation of receptors sensitive to 5-HT and nicotine receptors.

Animals

Blockade of neuronal tryptamine receptors by metoclopramide.

Metoclopramide (0.13, 0.51, 2.0 and 8.1 X 10(-6) M) caused parallel, rightward, shifts in the dose response curves to 5-HT on the isolated rabbit heart. A significant straight line relationship was found between log (5-HT dr--1) and log [metoclopramide] (molar) with a slope of 1.08 +/- 0.13 and giving a pA2 value of 7.20. Metoclopramide did not significantly alter responses to noradrenaline and was 575 times less effective as an inhibitor of DMPP than of 5-HT. The results indicate that metoclopramide is a potent, surmountable and selective antagonist of tryptamine receptors on rabbit cardiac sympathetic nerves.

Animals