N,N-Dimethyl-1H-indol-3-ethylamin

8.68

pKa = 8.68 (ethanol-water)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3000(SRC), determined from a structure estimation method(2), indicates that N,N-dimethyltryptamine is expected to have slight mobility in soil(SRC). The pKa of N,N-dimethyltryptamine is 8.68(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the neutral species from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 6.4X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(5). N,N-Dimethyltryptamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(6). Biodegradation data in soil were not available(SRC, 2012).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3000(SRC), determined from a structure estimation method(2), indicates that N,N-dimethyltryptamine is expected to adsorb to suspended solids and sediment(SRC). Volatilization of the neutral species from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 6.4X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A pKa of 8.68(5) indicates N,N-dimethyltryptamine will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 9(SRC), from an estimated log Kow of 1.94(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2012).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), N,N-dimethyltryptamine, which has an estimated vapor pressure of 3.1X10-4 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase N,N-dimethyltryptamine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 27 minutes(SRC), calculated from its rate constant of 2.8X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase N,N-dimethyltryptamine may be removed from the air by wet or dry deposition(SRC). N,N-Dimethyltryptamine does not contains chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

N,N-Dimethyltrytamine has been detectioned, not quantified in various plants(1).[Table#7963]

Dimethyltryptamine has been identified in the leaves of the tropical shrub Psychotria viridis (Rubiaceae) which is native to Central and South America(1). An Australian perennial pasture grass, Phalaris aquatica L., contains dimethyltryptamine in the leaves(2,3).

Dimethyltrytamine was detected, not quantified in Acacia senegal (L.) also known as gum Arabic, gum Arabic tree, kher, Senegal gum, Sudan gum arabic(1).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of N,N-dimethyltryptamine can be estimated to be 3000(SRC). According to a classification scheme(2), this estimated Koc value suggests that N,N-dimethyltryptamine is expected to have slight mobility in soil. The pKa of N,N-dimethyltryptamine is 8.68(3), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

N,N-Dimethyltryptamine occurs naturally in plants with halucinogenic properties and has been isolated from the leaves of Prestonia amazonica, Haemadictyon amazonicum, and Apocynaceae(1). It also occurs in Anadenanthera sp. and Banisteriopsis caapi, among others(2).

/HUMAN EXPOSURE STUDIES/ In a controlled study on 38 volunteers the effects of 250 ug/kg N,N-dimethyltryptamine (DMT) i.m. on objective and performance tests measuring psychoticism according to Eysenck were assessed. The hypothesis was tested that subjects treated with DMT (N = 26) differ from those receiving placebo (N = 12) in the same way as endogenous psychotics differ from normals. Confirmation was obtained in 7 out of 19 variables, most of which may be considered as tests of concentration. ...

/HUMAN EXPOSURE STUDIES/ ... A total of 15 healthy volunteers participated in a randomized, double-blind, crossover study with a low and a high dose of /dimethyltryptamine (DMT)/ and S-ketamine, which elicited subtle 'prepsychotic' or full-blown psychotic symptoms (low and high dose, respectively). Nine subjects completed both experimental days with the two doses of both drugs. Overall, both hallucinogens slowed down reaction times dose dependently (DMT >S-ketamine) and DMT diminished the general response facilitating (alerting) effect of spatially neutral cues. Inhibition of Return (IOR), that is, the normal reaction time disadvantage for validly cued trials with exogenous cues and long cue target intervals, was blunted after both doses of DMT...

/HUMAN EXPOSURE STUDIES/ /Investigators/ describe the subjective effects of graded doses of N,N-dimethyltryptamine (DMT), an endogenous hallucinogen and drug of abuse, in a group of experienced hallucinogen users. ... Twelve highly motivated volunteers received two doses (0.04 and 0.4 mg/kg) of intravenous (IV) dimethyltryptamine fumarate "nonblind," before entering a double-blind, saline placebo-controlled, randomized study using four doses of IV DMT. Subjects were carefully interviewed after resolution of drug effects, providing thorough and systematic descriptions of DMT's effects. ... Psychological effects of IV DMT began almost immediately after administration, peaked at 90 to 120 seconds, and were almost completely resolved by 30 min. This time course paralleled DMT blood levels previously described. Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate, and included a rapidly moving, brightly colored visual display of images. Auditory effects were less common. "Loss of control," associated with a brief, but overwhelming "rush," led to a dissociated state, where euphoria alternated or coexisted with anxiety. These effects completely replaced subjects' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness. Lower doses, 0.1 and 0.05 mg/kg, were primarily affective and somaesthetic, while 0.1 mg/kg elicited the least desirable effects. ... /Dimethyltryptamine fumarate/

/HUMAN EXPOSURE STUDIES/ To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, /the authors/ generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures... /Dimethyltryptamine fumarate/

For more Human Toxicity Excerpts (Complete) data for N,N-Dimethyltryptamine (9 total), please visit the HSDB record page.

An estimated BCF of 9 was calculated in fish for N,N-dimethyltryptamine(SRC), using an estimated log Kow of 1.94(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Henry's Law constant for N,N-dimethyltryptamine is estimated as 6.4X10-10 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that the neutral species is expected to be essentially nonvolatile from water and moist soil surfaces(2). A pKa of 8.68(3) indicates N,N-dimethyltryptamine will exist partially in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. N,N-Dimethyltryptamine is not volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.1X10-4 mm Hg(SRC), determined from a fragment constant method(4).

/LABORATORY ANIMALS: Neurotoxicity/ ... Dimethyltryptamine caused a dose-dependent decrease in the amplitude of the response evoked by stimulation of the optic chiasm as recorded in the lateral geniculate nucleus and the visual cortex. Dimethyltryptamine had no significant effect on antidromically evoked potentials in the lateral geniculate nucleus or potentials in the visual cortex produced by optic radiation stimulation. ...

/BEHAVIORAL STUDIES/ The /authors/ examined the role of the spinal cord and the brain in mediating the effects of the hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) on the acoustic startle response in the rat. Systemic administration of these agents, which distributes to both the brain and spinal cord, produced opposite effects, as DMT depressed and 5-MeODMT increased acoustic startle. However, when administered directly into the lateral ventricle in the forebrain (intraventricular administration) 5-hydroxytryptamine (5-HT), DMT and 5-MeODMT all depressed acoustic startle, DMT and 5-MeODMT being about equipotent in this regard. In contrast, when administered directly into the spinal cord subarachnoid space (intrathecal administration), 5-HT and 5-MeODMT increased startle, whereas DMT was without effect. In another series of studies, the effects of systemically-administered DMT and 5-MeODMT on the "startle" elicited by electrical stimulation of the nucleus reticularis pontis caudalis (RPC) were determined. Since the RPC is the last nucleus of the primary startle circuit before the spinal cord, agents which act downstream from the RPC (i.e., in the lower brainstem and spinal cord) would be expected to alter RPC-elicited "startle," while agents which act upstream from the RPC would be without effect. Given systemically, 5-MeODMT markedly increased RPC-elicited "startle" while DMT was without effect. These data indicate that DMT and 5-MeODMT are equipotent in depressing startle through actions in the brain. In contrast, the difference in the effects of DMT and 5-MeODMT on acoustic startle is related to the spinal excitatory effects of 5-MeODMT which DMT does not possess. ...

/BEHAVIORAL STUDIES/ Rats were tested for shock elicited fighting under various doses of N,N-dimethyltryptamine (0.12, 0.25, 0.50, 1.0, 4.0, 8.0 mg/kg) and 5-methoxy-N,N-dimethyltryptamine (0.06, 0.12, 0.5, 2.0 mg/kg). Both drugs produced an inhibition of fighting at higher doses but no significant effects at lower doses. The effects of these drugs on shock elicited fighting, as well as on other behaviors, thus differ from those of another indole hallucinogen, d-lysergic acid diethylamide, and are discussed in relation to their effects on single unit activity of the raphe-serotonin system and their interaction with other neurotransmitter systems.

/BEHAVIORAL STUDIES/ ... /The authors/ ... report behavioral effects of DMT in rodents and their manipulation by drugs acting on cerebral monoamine pathways. DMT (0.5-8.0 mg/kg i.p.) administered to male Swiss S mice (20-25 g) induced a dose-dependent hyperactivity syndrome comprising increased locomotor activity accompanied by prostration, hind-limb abduction, tremor, Straub tail, retropulsion, jerking and vocalization. Onset of activity occurred within 5 min but was of short duration (20-40 min)...Administration of DMT (0.5-35 mg/kg) to male Wistar rats (200-300 g) produced a similar dose dependent behavioral syndrome to that seen in mice. ... /Investigators/ suggest that the DMT-induced behavioral syndrome comprises two components. One consists of increased motor activity and can be manipulated by drugs acting on cerebral 5-HT and dopamine receptors. The other behavioral changes, however do not appear to be mediated via a monoamine pathway.

For more Non-Human Toxicity Excerpts (Complete) data for N,N-Dimethyltryptamine (10 total), please visit the HSDB record page.

The urinary excretion of N,N-dimethyltryptamine (DMT) was higher in patients with severe liver disease than in normal subjects. This difference remained significant when patients with all grades of hepatic encephalopathy were excluded. Patients with liver disease whose mental states were normal excreted amounts of DMT similar to those of patients with a hospital diagnosis of schizophrenia.

The incidence and quantities of dimethyltryptamine and O-methylbufotenine were studied in the cerebrospinal fluid of patients suffering acute schizophrenic illnesses and in surgical and neurological control groups. Some schizophrenic patients have higher levels of both amines than do controls, though the differences in distribution did not reach statistical significance in the sample studied. ...

The rate constant for the vapor-phase reaction of N,N-dimethyltryptamine with photochemically-produced hydroxyl radicals has been estimated as 2.8X10-10 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 27 minutes at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). N,N-Dimethyltryptamine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). N,N-Dimethyltryptamine does not contain chromophores that absorb at wavelengths >290 nm(2), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Following intraperitoneal administration, 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine are subject to both a very rapid uptake into, and clearance from, all tissues examined. The current studies in vivo confirm previous in vitro observations that the routes involved in the metabolism of these compounds include oxidative deamination, N-demethylation, O-demethylation, and N-oxidation. The analysis of metabolic profiles in various tissues led to the identification of the N-oxides as major metabolites...

... /From/ ... urine samples collected from three individuals that were administered ayahuasca ... /authors/ show that the major metabolite of the hallucinogenic component of ayahuasca, N,N-dimethyltryptamine (DMT), is the corresponding N-oxide... Further, very little DMT was detected in urine, despite the inhibition of monoamine oxidase afforded by the presence of the harmala alkaloids in ayahuasca. ...

Behavioral aspects and metabolic fate of N,N-dimethyltryptamine (DMT) were studied in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), iproniazid or chlorpromazine (CPZ.). ... Dose-dependent increases with rapid uptake and disappearance in the brain, plasma and hepatic levels of DMT were measured with doses of 10 and 25 mg/kg DMT. ... It is concluded that DMT is metabolized chiefly by monoamine oxidase rather than by drug-metabolizing hepatic microsomal enzymes and that DMT-induced behavioral effects are due to the parent compound rather than its metabolite.

Studies were conducted using tritiated DMT and DMT-N-oxide (DMT-NO), and metabolites were identified and quantified using thin-layer chromatography and liquid scintillation counting techniques. Metabolite confirmation was obtained by incubation of alpha,alpha,beta,beta-tetradeutero-DMT (DDMT) with whole brain homogenate followed by combined gas chromatographic/mass spectrometric analyses. The metabolites of DMT were identified as indoleacetic acid (IAA), DMT-NO, N-methyltryptamine (NMT), 2-methyl-1,2,3,4-tetrahydro-beta-carboline (2-MTHBC), tryptamine (TA) and 1,2,3,4- tetrahydro-beta-carboline (THBC). DMT-NO was metabolized to give DMT, NMT, IAA and 2-MTHBC. Formation of these metabolites from DMT-NO was stimulated by anaerobic incubation. ...

Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise.

Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.

(14)C-DMT accumulates in rat brain cortical slices incubated at 37 °C. ... Most of the accumulated (14)C-DMT was associated with the cytoplasmic fraction. Of the portion associated with the crude mitochondrial fraction, 54.4% was associated with nerve-ending fraction.

The hallucinogenic substance N',N'-dimethyltryptamine and its precursor N-methyltryptamine were found in 24-hr specimens of urine from 19 normal human subjects; the mean excretion rates were 386 ng 24 hr(-1) and 856 ng 24 hr(-1) respectively. The urinary excretion of both compounds was unrelated to age, sex, urinary volume, or creatinine, nor was any consistent diurnal pattern observed. Rates for the mono and dimethylated compounds were not correlated. Diet and the intestinal flora were excluded as a source of urinary dimethyltryptamine. Administration to 4 subjects of sufficient ammonium chloride to /decrease/ the /pH/ of the urine caused a transient increase in dimethyltryptamine excretion but no consistent increase in the rate for N-methyltryptamine. Acidification of the urine did not appear to be the determining factor in this result since in one subject the same drop in urinary pH was achieved by feeding methionine without any increase in dimethyltryptamine excretion.

... Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo. Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 hr, involving perceptual modifications and increases in ratings of positive mood and activation. ...Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/mL and 17.44 ng/mL, respectively. Tmax (median) was observed at 1.5 hr after both doses. The Tmax for DMT coincided with the peak of subjective effects. ...

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with (11)C and its regional distribution in rat brain studied. (11)C-DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of (11)C-DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. ...

For more Absorption, Distribution and Excretion (Complete) data for N,N-Dimethyltryptamine (8 total), please visit the HSDB record page.