Dimethyltryptamine levels in blood of schizophrenic patients and control subjects

Angrist, Burt; Gershon, Samuel; Sathananthan, Gregory; Walker, Robert; Lopez-Ramos, B.; Mandel, L; Vandenheuvel, W.J.A.

doi:10.1007/bf00428697

Cited by 42 publications

(6 citation statements)

References 5 publications

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“…N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) are substances used as models for the study of psychosis as they mimic schizophrenia in many aspects (Gillin et al, 1976;Fischer, 1974;Appel and Freedman, 1965;Wyatt et al, 1973Wyatt et al, , 1974Jacobsen, 1963;Domino, 1975). DMT has been postulated and sometimes identified as being an endogenous substance (Lu et al, 1974;Corbett et al, 1978;Appel and Freedman, 1965;Narasimhachari et al, 1971;Vogel and Evans, 1977;Oon et al, 1977;Lord et al, 1977;Bloom et al, 1976;Marx, 1976;Angrist et al, 1976). Similarly, an endogenous ligand of a putative LSD-serotonin receptor has been described in the cerebrospinal fluid of unmedicated psychotic patients (Mehl et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Naloxone enhancement of DMT and LSD-25 induced suppression of food-rewarded bar pressing behavior in the rat

et al. 1979

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The narcotic antagonist naloxone was tested to determine its possible interaction with N,N-dimethyltryptamine (DMT) and lysergic acid diethylamide-25 (LSD) in adult male Holtzman rats trained to press a bar on a fixed-ratio four schedule (FR4), i.e., every fourth press earned a reward of 0.01 ml sugar sweetened milk. LSD (0.1 mg/kg) or increasing doses of DMT (1.0, 3.2, and 10.0 mg/kg) were administered i.p. to disrupt food-rewarded fixed ratio bar pressing in a dose related fashion. Pretreatment (5--10 min) with behaviorally ineffective doses of naloxone (1.0--5.6 mg/kg) dramatically enhanced the effects of DMT and LSD. The content of DMT in the brain and liver of rats injected with DMT alone (10 mg/kg) and with a 5 min pretreatment of naloxone (3.2 mg/kg) was determined by radiochemical analysis at 30 and 90 min after 14C-DMT injection. There was no significant difference for either brain or liver 14C-DMT levels when control DMT rats were compared with the naloxone pretreated rats. These results seem to rule out interference by naloxone with the metabolism of DMT as a mechanism of the observed behavioral potentiation.

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Section: Discussionmentioning

confidence: 99%

Naloxone enhancement of DMT and LSD-25 induced suppression of food-rewarded bar pressing behavior in the rat

et al. 1979

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“…5-MeO-DMT is synthesized and distributed for recreational purposes (Yu, 2008) and intoxications have been reported (Brush et al, 2004;Sklerov et al, 2005). Early reports suggested 5-MeO-DMT as a possible endogenous psychotoxin and several studies indicated its potential involvement in schizophrenia (Benington et al, 1965;Angrist et al, 1976;Gillin and Wyatt, 1976). In 2010 the Deputy Administrator of the Drug Enforcement Administration (DEA) placed 5-MeO-DMT into schedule I of the Controlled Substances Act (Drug Enforcement Administration (DEA), 2010).…”

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confidence: 99%

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs

Riga

Sòria

Tudela

et al. 2014

Int. J. Neuropsychopharm.

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5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

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“…Transmethylation produces N -methyltryptamine (MMT) and N , N -dimethyltryptamine (DMT). DMT is found in trace amounts in humans and other animals. ,− For a thorough review of the synthesis of DMT, its regulation, and its metabolism, see ref . Recently, Barker and colleagues, using microdialysis techniques, detected DMT in real time in the pineal glands of living rats …”

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Noncompetitive Inhibition of Indolethylamine-N-methyltransferase by N,N-Dimethyltryptamine and N,N-Dimethylaminopropyltryptamine

et al. 2014

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Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT is produced via the action of INMT on the endogenous substrates tryptamine and S-adenosyl-l-methionine (SAM). The biological, biochemical, and selective small molecule regulation of INMT enzyme activity remain largely unknown. Kinetic mechanisms for inhibition of rabbit lung INMT (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were determined. After Michaelis–Menten and Lineweaver–Burk analyses had been applied to study inhibition, DMT was found to be a mixed competitive and noncompetitive inhibitor when measured against tryptamine. The novel tryptamine derivative, N-[2-(1H-indol-3-yl)ethyl]-N′,N′-dimethylpropane-1,3-diamine (propyl dimethyl amino tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive mechanism when measured against tryptamine with a Ki of 84 μM. No inhibition by PDAT was observed at 2 mM when it was tested against structurally similar Class 1 methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT) and human nicotinamide-N-methyltransferase (hNNMT), indicating selectivity for INMT. The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site. In silico analyses using the computer modeling software Autodock and the rabINMT sequence threaded onto the human INMT (hINMT) structure (Protein Data Bank entry 2A14) identified an N-terminal helix–loop–helix non-active site binding region of the enzyme. The energies for binding of DMT and PDAT to this region of rabINMT, as determined by Autodock, were −6.34 and −7.58 kcal/mol, respectively. Assessment of the allosteric control of INMT may illuminate new biochemical pathway(s) underlying the biology of INMT.

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Dimethyltryptamine levels in blood of schizophrenic patients and control subjects

Cited by 42 publications

References 5 publications

Naloxone enhancement of DMT and LSD-25 induced suppression of food-rewarded bar pressing behavior in the rat

Naloxone enhancement of DMT and LSD-25 induced suppression of food-rewarded bar pressing behavior in the rat

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs

Noncompetitive Inhibition of Indolethylamine-N-methyltransferase by N,N-Dimethyltryptamine and N,N-Dimethylaminopropyltryptamine

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