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A fatal overdose involving case by 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is reported. 5-MeO-DIPT and its two metabolites, 5-hydroxy-N,N-diisopropyltryptamine (5-OH-DIPT) and 5-methoxy-N-isopropyltryptamine (5-MeO-NIPT), were identified by LC-MS. The level of 5-MeO-DIPT, 5-OH-DIPT and 5-MeO-NIPT in blood and urine was 0.412, 0.327 and 0.020 microg/ml, and 1.67, 27.0 and 0.32 microg/ml, respectively. These blood and urine levels were higher than published data for such poisoning.

We devised a sensitive and simple method to determine alpha-methyltryptamine (AMT) and 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) in whole blood and urine, using gas chromatography-mass spectrometry (GC-MS). AMT and 5MeO-DIPT were extracted using an Extrelut column with an internal standard, bupivacaine, followed by derivatization with acetic anhydride. The derivatized extract was used for GC-MS analysis of EI-SIM mode. The calibration curves of AMT and 5MeO-DIPT were linear in the concentration range from 10 to 750 ng/ml in both blood and urine samples. The method detection limit (MDL) of AMT and 5MeO-DIPT were 1 ng/ml each in whole blood and 5 ng/ml each in urine. This method should be most useful to accurately determine the presence of these drugs in blood and urine in clinical and forensic cases.

Foxy is the colloquial name for the hallucinogen 5-ethoxy-diisopropyltryptamine (5-MeO-DIPT). A non-fatality involving a 23-year-old Caucasian man who ingested a capsule containing 5-MeO-DIPT is described. He presented to the Emergency Department, not with visual nor auditory hallucinations but with sensory hallucinations, that of formication and paranoia. He was observed and given supportive care for 4 h, then discharged without any known sequelae. Blood and urine were collected for laboratory analyses. Foxy and its metabolites were identified in urine by gas chromatography-mass spectrometry. The concentrations of 5-MeO-DIPT in the serum and urine were 0.14 and 1.6 microg/mL, respectively. The drug undergoes oxidative deamination to form 5-methoxy-indole acetic acid. The urinary concentration of this metabolite was 0.17 microg/mL. Also, the urine contained three other related compounds. Two of them have been described in a previous case of 5-MeO-DIPT ingestion as 5-methoxy-isopropyltryptamine (5-MeO-IPT) and 5-methoxy-diisopropyltryptamine-N'-oxide (5-MeO-DIPT-N'-oxide). The third compound was substantially present in the urine and was tentatively identified as 5-hydroxy-diisopropyltryptamine (5-OH-DIPT). Only the parent drug, 5-MeO-DIPT was detected in the serum sample.

Recent additions of designer tryptamines and phenethylamines to the Drug Enforcement Administration's schedule of controlled substances necessitate analytical procedures for their detection and quantitation. As specific immunoassays are not currently available and cross-reactivities with existing assays are unknown, a screening method based on gas chromatography-mass spectrometry was developed. The method was capable of measuring the pentafluoropropionic derivatives of a-methyltryptamine (AMT), N,N-dimethyltryptamine (DMT), 4-bromo-2,5-dimethoxy-beta-phenethylamine (2CB), N,N-dipropyltryptamine (DPT), 2,5-dimethyl-4-N-propylthio-beta-phenethylamine (2C-T-7), and 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DiPT). Separation was optimized to allow tentative identification of metabolites, which display common electron impact ionization fragmentation patterns. The screening method gave limits of detection between 5 and 10 ng/mL and demonstrated linearity between 50 and 1000 ng/mL. The method was successfully applied to blood and urine samples in suspected AMT intoxications. Confirmation of 5-MeO-DiPT in one of the subjects' urine was achieved using liquid chromatography-mass spectrometry (LC-MS). Quantitation by selected ion monitoring (SIM) yielded a urinary concentration of 229 ng/mL. The method was linear from 25 to 1500 ng/mL with a correlation coefficient of 0.995. The limit of detection was 5 ng/mL in urine on the LC-MS. Two additional peaks were observed and presumed to be metabolic products reported previously as 5-methoxy-N-isopropyltryptamine (5-MeO-iPT) and 5-methoxy-N,N-diisopropyltryptamine-N'-oxide (5-MeO-DiPT-N-oxide).

Picomole to femtomole per gland/ml levels of 5-methoxytryptamine (5MT) in the pineal gland and serum of the rat and quail were determined, in the absence of a monoamine oxidase inhibitor, by using the ultra-sensitive technique of capillary column gas chromatography/electron-capture negative ion chemical ionization mass spectrometry. Diurnal rhythms of pineal 5MT with high levels at mid-light and low levels at mid-dark were found in both species, while serum 5MT levels showed less or no diurnal variations. The definitive presence of 5MT in the pineal gland and blood circulation provides further evidence that it is potentially a neurohormone. Whether 5MT is implicated in the photoperiodic responses and/or other physiological functions of animals, however, remains to be investigated.

A liquid chromatographic analysis with electrochemical detection of 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxyindoleacetic acid and melatonin is described. Optimal elution conditions were determined by studying several variables: pH, buffer salt, counter ion and organic modifier. Measurement of 5-methoxyindoles in the pineal gland and plasma of hamsters has been performed after extraction. This method is specific and sensitive, and enables detection of 5-methoxyindoles in a pool of two hamster pineal glands. This is also the first time that these three 5-methoxyindoles have been measured simultaneously in plasma.

Pineal concentrations of 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxyindole acetic acid and melatonin were determined using high performance liquid chromatography following administration of different monoamine oxidase (MAO) inhibitors (clorgyline, pargyline and deprenyl) to golden hamsters. Plasma concentrations of 5-methoxytryptamine, 5-methoxytryptophol and melatonin were also measured following 5-methoxytryptamine administration to hamsters pretreated with MAO inhibitors. A significant increase in pineal and plasma 5-methoxytryptamine together with a decrease in 5-methoxytryptophol concentrations was observed after clorgyline or pargyline. In contrast, following deprenyl administration, no change in pineal and plasma 5-methoxyindoles was observed. These results indicate that monoamine oxidase A is responsible for oxidative deamination of 5-methoxytryptamine.

5-Methoxytryptamine (5-MT), 5-methoxytryptophol (5-ML) and melatonin (Mel) were measured in the plasma after 2, 5, and 8 weeks administration of 25 micrograms 5-MT to golden hamsters kept under long photoperiod. 5-MT showed a one compartment kinetic profile in the plasma with half lives of 14.8 min after 2 weeks, 15 min after 5 weeks and 19.1 min after 8 weeks. A rapid metabolism of 5-MT was shown, Mel and 5-ML being detected in the plasma following 5-MT administration. However it was also shown that the gonadal atrophy observed after 5-MT administration cannot be due to its metabolism into these 2 compounds. Indeed when exogenously administered at a dose generating the same plasma concentration as that observed after 5-MT, the gonadal regression observed after the association of 5-ML and Mel is much less than that observed after 5-MT. 5-MT is thus a compound of great physiological interest.

N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] has recently been synthesized and shown to antagonize the inhibitory effect of melatonin on the release of dopamine in vitro from the hypothalamus of female rats. In the present study the ability of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] to inhibit in vivo the following melatonin-mediated effects was investigated: (1) delayed sexual maturation of young male rats, (2) delayed sexual maturation of young female rats, (3) inhibition of ovulation in mature female rats and (4) re-establishment of oestrous cycles in adult female rats maintained in continuous light. The inhibitory effect of daily melatonin injections, given in the afternoon, on the growth of the prostate gland and seminal vesicles and on serum testosterone concentrations in young male rats was prevented by daily injections of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected]. Daily injections of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] alone did not affect sexual maturation of young rats. In young male rats treated through the drinking water with melatonin, the growth of the accessory sex organs, but not that of the testes, was delayed and serum concentrations of testosterone were lower than in untreated rats. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water increased serum concentrations of testosterone but did not significantly affect the weights of the accessory sex organs. Simultaneous administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] and melatonin through the drinking water prevented completely, in a dose-dependent manner, the melatonin-mediated decrease in epididymal weights and in serum concentrations of testosterone and partially inhibited the delayed growth of the prostate glands and seminal vesicles. In young female rats treated with melatonin through the drinking water for 30 days, the growth of the ovaries was inhibited and serum concentrations of oestradiol were lower than in untreated rats. The growth of the uterus was not significantly affected. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water did not significantly affect uterine and ovarian weights or oestradiol concentrations. Simultaneous administration of melatonin and N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] through the drinking water prevented completely the melatonin-mediated decrease in ovarian weights and in serum oestradiol concentrations. Ovulation during presumptive oestrus was prevented in adult female rats treated through the drinking water for 7 days with melatonin. Administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] alone did not significantly affect the average numbers of ova shed and corpora lutea present. Simultaneous administration of N-(2,4-dinitrophenyl)-5-methoxytryptamine [corrected] and melatonin prevented completely the melatonin-mediated inhibition of ovulation; the average number of ova shed was the same as in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Deacetylation of melatonin to 5-methoxytryptamine (5-MT) in vitro and in vivo was investigated in rat liver and brain tissue, using a gas chromatographic--mass spectrometric 5-MT assay method. In vitro incubation of liver but not brain (hypothalamic, Mesencephalic) slices with melatonin led to a concentration-dependent formation of small amounts of 5-MT; the conversion being 0.3--0.8%. In vivo administration of melatonin resulted in a dose-dependent formation of 5-MT in small quantities in the liver. The time course showed a peak maximum within 0.5 h, with a rapid decline; the half-life being about 1 h. 5-MT could be detected in both the blood and the hypothalamus after in vivo injection of melatonin. The time course of 5-MT in the blood was similar to that in the liver, but 5-MT could only be detected in the hypothalamus after large doses shortly after the melatonin injection. MAO had to be inhibited both in the in vitro and in vivo experiments in order to recover 5-MT, indicating that formed 5-MT is normally rapidly metabolised by MAO. It is concluded that a small fraction of melatonin can be converted to 5-MT by deacetylation (by aryl acylamidase) in the liver in vivo, constituting a minor pathway. Such a pathway could not be demonstrated in the brain. Trace amounts of 5-MT previously reported to be present in various tissues could originate from deacetylation of melatonin in the liver and possibly some other peripheral organs known to contain the deacetylating enzyme. The present results indicate that peripherally formed 5-MT, a psychoactive compound, is unlikely to have any effect on brain function under normal circumstances.

A method was developed for the separation by thin-layer chromatography of 14C-labelled 3-methoxy, 4-hydroxyphenethylamine, 3-hydroxy, 4-methoxyphenethylamine and 3,4-dimethoxyphenethylamine (DMPEA) after incubation of dopamine with catechol-O-methyltransferase (COMT) in lysates of human red blood cells (RBC). 14 C-methyl-S-adenosyl-menthionine was used as the methyl donor. Total COMT activity with noradrenaline or dopamine as substrates, respectively, and the pattern of 14C-methylated metabolites of dopamine were measured in RBC of 47 schizophrenic patients and in 34 control subjects. There were no differences between patients and controls. DMPEA was not formed by RBC in schizophrenic patients (or in controls), a finding which argues against the "pnk spot"/DMPEA hypothesis of schizophrenia. The methods used seem suitable for studies of other human disorders where COMT might be involved.