methoxydimethyltryptamines

Summary

Summary: Compounds that contain the biogenic monoamine tryptamine and are substituted with one methoxy group and two methyl groups. Members of this group include several potent serotonergic hallucinogens found in several unrelated plants, skins of certain toads, and in mammalian brains. They are possibly involved in the etiology of schizophrenia.

Top Publications

  1. Ahlenius S, Larsson K. Opposite effects of 5-methoxy-N,N-di-methyl-tryptamine and 5-hydroxytryptophan on male rat sexual behavior. Pharmacol Biochem Behav. 1991;38:201-5 pubmed
    ..kg-1 SC -30 min) had no effects of its own and did not interact with 5-HTP. The results suggest that stimulation of brain 5-HT1 or 5-HT2 receptors produces facilitation and inhibition, respectively, of the male rat sexual behavior...
  2. Forsstrom T, Tuominen J, Kärkkäinen J. Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS. Scand J Clin Lab Invest. 2001;61:547-56 pubmed
    ..Method, procedure, considerations, statistical evaluations and urine sample spectra are presented...
  3. Jiang X, Shen H, Mager D, Yu A. Pharmacokinetic interactions between monoamine oxidase A inhibitor harmaline and 5-methoxy-N,N-dimethyltryptamine, and the impact of CYP2D6 status. Drug Metab Dispos. 2013;41:975-86 pubmed publisher
    ..This PK model may be further employed to predict harmaline and 5-MeO-DMT PK interactions at various doses, define the impact of CYP2D6 status, and drive harmaline-5-MeO-DMT pharmacodynamics...
  4. Nabeshima T, Ishikawa K, Yamaguchi K, Furukawa H, Kameyama T. Phencyclidine-induced head-weaving observed in mice after ritanserin treatment. Eur J Pharmacol. 1987;139:171-8 pubmed
    ..These results indicate that PCP induces head-weaving by interacting with a 5-HT receptor (possibly of the 5-HT1 subtype) indirectly after 5-HT release and induces head-twitch by interacting with 5-HT2 receptors directly...
  5. Brunken W, Daw N. The effects of serotonin agonists and antagonists on the response properties of complex ganglion cells in the rabbit's retina. Vis Neurosci. 1988;1:181-8 pubmed
  6. Winter J, Petti D. The effects of 8-hydroxy-2-(di-n-propylamino)tetralin and other serotonergic agonists on performance in a radial maze: a possible role for 5-HT1A receptors in memory. Pharmacol Biochem Behav. 1987;27:625-8 pubmed
  7. Jackson H, Kitchen I. Behavioural profiles of putative 5-hydroxytryptamine receptor agonists and antagonists in developing rats. Neuropharmacology. 1989;28:635-42 pubmed
    ..Preliminary findings with (-)-pindolol, which was high affinity for 5-HT1-receptors, suggested that this subtype of receptor may play a role in hyperlocomotion induced by RU 24969.(ABSTRACT TRUNCATED AT 250 WORDS)..
  8. Fone K, Johnson J, Bennett G, Marsden C. Involvement of 5-HT2 receptors in the behaviours produced by intrathecal administration of selected 5-HT agonists and the TRH analogue (CG 3509) to rats. Br J Pharmacol. 1989;96:599-608 pubmed
    ..This suggests that bulbospinal 5-HTergic neurones are not involved in the production of these TRH analogue-induced behaviours and that the 5-HT2 receptors which mediate these behaviours are not located in the spinal cord...
  9. Traversa U, Puppini P, Florio C, Vertua R. Effects of an atypical barbiturate (valofan) on spontaneous and stimulated locomotor activity and on brain serotonin metabolism in mice. Farmaco Sci. 1987;42:755-66 pubmed
    ..We can therefore suggest that valofan manifests its central effects by an unclear mechanism which cannot completely be accounted for its metabolic effects on cerebral serotonin and dopamine...

More Information

Publications62

  1. Glennon R, Lee M, Rangisetty J, Dukat M, Roth B, Savage J, et al. 2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors. J Med Chem. 2000;43:1011-8 pubmed
    ..e., 10: K(i) = 20 nM) but lacks agonist character. 2-Substituted tryptamines, then, might allow entry to a novel class of 5-HT(6) agonists and antagonists...
  2. Duvvuri V, Risbrough V, Kaye W, Geyer M. 5-HT1A receptor activation is necessary for 5-MeODMT-dependent potentiation of feeding inhibition. Pharmacol Biochem Behav. 2009;93:349-53 pubmed publisher
    ..Our findings hint at a mechanistic role for increased 5-HT(1A) receptor activation in restricting-type AN. Further implications for the interplay between anxiety and feeding inhibition in AN are discussed...
  3. Glennon R, De Vry J, Spencer D, Glaser T. Stimulus properties of tiflucarbine: a novel antidepressant agent. Pharmacol Biochem Behav. 1990;37:769-71 pubmed
    ..Although two-thirds of the animals were disrupted, 10 mg/kg of tiflucarbine resulted in stimulus generlization in the 5-OMe DMT-trained animals. It is concluded that tiflucarbine is most likely a nonselective 5-HT agonist...
  4. Schreiber R, De Vry J. Studies on the neuronal circuits involved in the discriminative stimulus effects of 5-hydroxytryptamine1A receptor agonists in the rat. J Pharmacol Exp Ther. 1993;265:572-9 pubmed
    ..p. NAN-190) attenuated the discriminative stimulus effects of 8-OH-DPAT injected i.p. (0.1 mg/kg), into the DRN (10 micrograms) or into the hippocampus (2 x 10 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)..
  5. Yadin E, Friedman E, Bridger W. Spontaneous alternation behavior: an animal model for obsessive-compulsive disorder?. Pharmacol Biochem Behav. 1991;40:311-5 pubmed
    ..Serotonergic manipulations of spontaneous alternation may be a simple animal model for the perseverative symptoms or indecisiveness seen in people diagnosed with OCD...
  6. Eison A, Wright R. 5-HT1A and 5-HT2 receptors mediate discrete behaviors in the Mongolian gerbil. Pharmacol Biochem Behav. 1992;43:131-7 pubmed
    ..0125-0.2 mg/kg, SC). RHBS behavior is also potently inhibited by pretreatment with the selective 5-HT1A agonist 8-OH-DPAT (0.005-0.04 mg/kg, SC), demonstrating a 5-HT1A/5-HT2 receptor subtype interaction.(ABSTRACT TRUNCATED AT 250 WORDS)..
  7. Eide P, Hole K, Berge O, Broch O. 5-HT depletion with 5,7-DHT, PCA and PCPA in mice: differential effects on the sensitivity to 5-MeODMT, 8-OH-DPAT and 5-HTP as measured by two nociceptive tests. Brain Res. 1988;440:42-52 pubmed
    ..Alternatively, the three 5-HT depleting agents may produce a qualitatively different reduction of 5-HT...
  8. Weil A, Davis W. Bufo alvarius: a potent hallucinogen of animal origin. J Ethnopharmacol. 1994;41:1-8 pubmed
    ..These experiments are the first documentation of an hallucinogenic agent from the animal kingdom, and they provide clear evidence of a psychoactive toad that could have been employed by Precolumbian peoples of the New World...
  9. Gomez Mancilla B, Bedard P. Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys. Clin Neuropharmacol. 1993;16:418-27 pubmed
    ..However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea...
  10. Halberstadt A. Behavioral and pharmacokinetic interactions between monoamine oxidase inhibitors and the hallucinogen 5-methoxy-N,N-dimethyltryptamine. Pharmacol Biochem Behav. 2016;143:1-10 pubmed publisher
    ..The present results confirm that 5-MeO-DMT can disrupt PPI by activating 5-HT2A, and indicate that MAOIs alter 5-MeO-DMT pharmacodynamics by increasing its accumulation in the central nervous system. ..
  11. Eide P, Hole K. Acute and chronic treatment with selective serotonin uptake inhibitors in mice: effects on nociceptive sensitivity and response to 5-methoxy-N,N-dimethyltryptamine. Pain. 1988;32:333-40 pubmed
    ..Different modulation of different 5-HT receptor subpopulations by these compounds may possibly contribute to the test-dependent results...
  12. Ikeda A, Sekiguchi K, Fujita K, Yamadera H, Koga Y. 5-methoxy-N,N-diisopropyltryptamine-induced flashbacks. Am J Psychiatry. 2005;162:815 pubmed
  13. Berger A, Ramirez A. Hypotensive spinal serotonergic effect. Are S1 or S2 receptors involved?. Hypertension. 1988;11:I182-5 pubmed
    ..The results suggest that the hypotensive effect obtained after the spinal serotonergic activation involves serotonin receptors of the S2 type...
  14. Cheetham S, Heal D. Evidence that RU 24969-induced locomotor activity in C57/B1/6 mice is specifically mediated by the 5-HT1B receptor. Br J Pharmacol. 1993;110:1621-9 pubmed
    ..RU 24969 did not alter dopamine, dihydroxyphenylacetic acid or homovanillic acid concentrations in the nucleus accumbens suggesting that the dopaminergic neurones terminating there are not directly involved...
  15. Eichelbaum M. In search of endogenous CYP2D6 substrates. Pharmacogenetics. 2003;13:305-6 pubmed
  16. Schechter M. Serotonergic mediation of fenfluramine discriminative stimuli in fawn-hooded rats. Life Sci. 1997;60:PL83-90 pubmed
    ..Suggestions to explain these results are offered and discussed...
  17. Matsumoto K, Mizowaki M, Takayama H, Sakai S, Aimi N, Watanabe H. Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice. Pharmacol Biochem Behav. 1997;57:319-23 pubmed
    ..These results indicate that stimulation of postsynaptic alpha 2-adrenoceptor, blockade of 5-HT2A receptors, or both, are involved in suppression of 5-HT2A receptor-mediated head-twitch response by mitragynine...
  18. Ahlenius S, Hillegaart V, Wijkström A. Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration in the rat. J Pharm Pharmacol. 1990;42:285-8 pubmed
  19. Fulginiti S, Vigliecca N, Minetti S. Acute ethanol intoxication during pregnancy: postnatal effects on the behavioral response to serotonin agents. Alcohol. 1992;9:523-7 pubmed
    ..These results demonstrated that acute administration of ethanol on GD 8 induced long-lasting changes in the functioning of central serotonergic systems...
  20. Sargent T, Braun U, Braun G, Kusubov N, Bristol K. Cerebral and peripheral demethylation of psychotomimetics measured by expired 14CO2. Int J Rad Appl Instrum B. 1989;16:91-9 pubmed
    ..2,4,5-Trimethoxyphenalkylamines were demethylated less in the brain than peripherally, markedly so at the p-methoxy position, suggesting a possible biochemical site for endogenous induction of psychosis...
  21. Wang H, Grahame Smith D. The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat and mouse--3. Quinine. Neuropharmacology. 1992;31:425-31 pubmed
    ..This conclusion is also discussed in relation to the actions of lithium and electroconvulsive shock on 5-HT function in brain and the treatment of manic-depressive disease...
  22. Keller E, Cancela L, Molina V, Orsingher O. Lack of adaptive changes in 5-HT sites in perinatally undernourished rats after chronic stress: opioid influence. Pharmacol Biochem Behav. 1994;47:789-93 pubmed
    ..A possible deficiency in the functional role of the opiate system involved in the process of adaptation to chronic stress in early undernourished rats is suggested...
  23. Clement M, Mccall R. Pharmacological characterization of medullary serotonin neurons. Brain Res. 1991;542:205-11 pubmed
    ..In addition, the data suggest that the firing rate of medullary 5-HT neurons is regulated in part by a tonic excitatory noradrenergic input...
  24. Chojnacka Wójcik E. Modulation of the 5-HT1C receptor-mediated behavior by 5-HT2, but not 5-HT1A, receptor activation. Pol J Pharmacol Pharm. 1992;44:427-36 pubmed
    ..The obtained results permit an assumption that a functional interaction exists between 5-HT1C- and 5-HT2-receptors, but not between 5-HT1C- and 5-HT1A-ones...
  25. Nash J, Meltzer H, Gudelsky G. Selective cross-tolerance to 5-HT1A and 5-HT2 receptor-mediated temperature and corticosterone responses. Pharmacol Biochem Behav. 1989;33:781-5 pubmed
    ..These selective changes in receptor responsiveness following the chronic administration of these 5-HT agonists further establishes the independence of 5-HT1A and 5-HT2 receptor-mediated pharmacological effects...
  26. Kubota M, Ueno K, Yamano M, Kitagawa H. [Changes in 5-HT2 receptor density induced by repeated treatment with 5-HT uptake inhibitor or 5-HT agonist]. Yakubutsu Seishin Kodo. 1989;9:289-92 pubmed
    ..The 5-HT2 receptor density was decreased by repeated treatment with these respective drugs. So it may be supposed that the reduction of 5-HT2 receptor binding is induced not only by 5-HT antagonists but also by 5-HT agonists...
  27. Nash J, Meltzer H. Effect of gepirone and ipsapirone on the stimulated and unstimulated secretion of prolactin in the rat. J Pharmacol Exp Ther. 1989;249:236-41 pubmed
    ..In light of other evidence that GEP has D2 antagonist effects in vivo, we hypothesize that GEP and perhaps IPS are partial dopamine agonists which may contribute to their antianxiety and/or antidepressant properties...
  28. Sheets L, Cook L, Reiter L. Serotonergic modulation of the acoustic startle response in rats during preweaning development. Pharmacol Biochem Behav. 1989;33:415-22 pubmed
    ..Generalized depletion of 5-HT by 80-90% in whole-brain and spinal cord, using p-chlorophenylalanine (PCPA, 300 mg/kg 24 hr prior to testing), did not alter ASR amplitude at any age.(ABSTRACT TRUNCATED AT 250 WORDS)..
  29. Ohi K, Mikuni M, Takahashi K. Stress adaptation and hypersensitivity in 5-HT neuronal systems after repeated foot shock. Pharmacol Biochem Behav. 1989;34:603-8 pubmed
    ..The results of beta-adrenergic receptor binding determined simultaneously were also discussed with reference to previous reports of stress-induced reduction in beta-adrenergic receptor density...
  30. Loscher W, Witte U, Fredow G, Ganter M, Bickhardt K. Pharmacodynamic effects of serotonin (5-HT) receptor ligands in pigs: stimulation of 5-HT2 receptors induces malignant hyperthermia. Naunyn Schmiedebergs Arch Pharmacol. 1990;341:483-93 pubmed
    ..5-HT2 antagonists, such as ketanserin or ritanserin, are capable of counteracting the fatality of this syndrome...
  31. Dabire H, Cherqui C, Schmitt H. [Hemodynamic profile of 8-OH-DPAT and 5-HT1 agonists in the anesthetized dog]. Arch Mal Coeur Vaiss. 1990;83:1191-4 pubmed
    ..The increase in PAP induced by 5-MeODMT, RU 24969 and--to a lesser extent--5-CT, may be due to a direct stimulation of 5-HT2 receptors. However, a 5-HT1 component could not be ruled out...
  32. Winter J, Amorosi D, Rice K, Cheng K, Yu A. Stimulus control by 5-methoxy-N,N-dimethyltryptamine in wild-type and CYP2D6-humanized mice. Pharmacol Biochem Behav. 2011;99:311-5 pubmed publisher
    ..In both groups of mice, harmaline was found to enhance the stimulus effects of 5-MeO-DMT...
  33. Tanaka E, Baba N, Toshida K, Suzuki K. Evidence for 5-HT2 receptor involvement in the stimulation of preovulatory LH and prolactin release and ovulation in normal cycling rats. Life Sci. 1993;52:669-76 pubmed
    ..The present study suggests that 5-HT stimulates preovulatory LH and PRL surge and ovulation via 5-HT2 receptor under physiological conditions and that the effect of 5-HT depends on the critical period and the 24-hour periodicity...
  34. Cherqui C, Dabire H, Fournier B, Schmitt H. Participation of sympathetic and vagal tones in the hypotensive and bradycardic effects of some 5-HT1-like receptor agonists in the rat. Arch Int Pharmacodyn Ther. 1988;296:18-28 pubmed
  35. Cuadra G, Molina V. Different behavioral reactivity of 5-HT1 sites between killer and non-killer rats after midbrain raphe lesion. Acta Physiol Pharmacol Latinoam. 1989;39:91-100 pubmed
    ..Finally, the decreased reactivity of 5-HT1 sites may be an index of a lower 5-HT neurotransmission and could therefore provide an explanation of the appearance of muricidal activity in some but not in all the lesioned rats...
  36. Roth B, Choudhary M, Khan N, Uluer A. High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model. J Pharmacol Exp Ther. 1997;280:576-83 pubmed
    ..These results are consistent with recent models of G protein-receptor functioning (e.g., modified ternary complex model) that predict that additional transition states of the receptor-ligand complex are essential for agonist efficacy...
  37. Stewart B, Jenner P, Marsden C. Induction of purposeless chewing behaviour in rats by 5-HT agonist drugs. Eur J Pharmacol. 1989;162:101-7 pubmed
    ..These data support the role of 5-HT receptors in the mediation of purposeless chewing behaviour and suggest an interaction between brain 5-HT and acetylcholine systems...
  38. Dey S. Physical exercise as a novel antidepressant agent: possible role of serotonin receptor subtypes. Physiol Behav. 1994;55:323-9 pubmed
    ..This adaptive supersensitivity of 5-HT2 receptor is also seen after various antidepressant treatments and may play an important role in mediating the antidepressant action of exercise...
  39. Lima L, Salazar M, Trejo E. Modulation of 5HT1A receptors in the hippocampus and the raphe area of rats treated with clonazepam. Prog Neuropsychopharmacol Biol Psychiatry. 1993;17:663-77 pubmed
    ..5. These changes could be related to the anxyolitic activity or the withdrawal symptoms of benzodiazepines...
  40. Sitaram B, Lockett L, McLeish M, Hayasaka Y, Blackman G, McLeod W. Gas chromatographic-mass spectroscopic characterisation of the psychotomimetic indolealkylamines and their in vivo metabolites. J Chromatogr. 1987;422:13-23 pubmed
    ..We now describe the combination of liquid chromatography with gas chromatography-mass spectrometry for the unequivocal verification of a number of structurally characteristic metabolites of the psychotomimetic indolealkylamines...
  41. Schechter L, Smith D, Rosenzweig Lipson S, Sukoff S, Dawson L, Marquis K, et al. Lecozotan (SRA-333): a selective serotonin 1A receptor antagonist that enhances the stimulated release of glutamate and acetylcholine in the hippocampus and possesses cognitive-enhancing properties. J Pharmacol Exp Ther. 2005;314:1274-89 pubmed
    ..m.) in marmosets. The heterosynaptic nature of the effects of lecozotan imbues this compound with a novel mechanism of action directed at the biochemical pathologies underlying cognitive loss in Alzheimer's disease...
  42. Krebs Thomson K, Ruiz E, Masten V, Buell M, Geyer M. The roles of 5-HT1A and 5-HT2 receptors in the effects of 5-MeO-DMT on locomotor activity and prepulse inhibition in rats. Psychopharmacology (Berl). 2006;189:319-29 pubmed
    ..The present study examined the effects of 5-MeO-DMT in rats using the Behavioral Pattern Monitor (BPM), which enables analyses of patterns of locomotor activity and exploration, and the prepulse inhibition of startle (PPI) paradigm...
  43. Yamazaki J, Fukuda H, Nagao T, Ono H. 5-HT2/5-HT1C receptor-mediated facilitatory action on unit activity of ventral horn cells in rat spinal cord slices. Eur J Pharmacol. 1992;220:237-42 pubmed
    ..This suggests that 5-HT2 and/or 5-HT1C receptors are involved in the facilitatory effects of 5-HT receptor agonists on the synaptic activity of ventral horn cells...
  44. Fujii E, Nomoto T, Muraki T. Effects of two 5-hydroxytryptamine agonists on head-weaving behaviour in streptozotocin-diabetic mice. Diabetologia. 1991;34:537-41 pubmed
    ..These results suggest that the reduced response to 5-HT1 agonists in streptozotocin-diabetic mice may be caused by the depletion of insulin...
  45. Bourke C, Carrigan M, Dixon R. The pathogenesis of the nervous syndrome of Phalaris aquatica toxicity in sheep. Aust Vet J. 1990;67:356-8 pubmed
  46. Peters D. Effects of maternal stress during different gestational periods on the serotonergic system in adult rat offspring. Pharmacol Biochem Behav. 1988;31:839-43 pubmed
    ..Our findings also provide further evidence that stress during the final trimester of pregnancy may have serious adverse effects on fetal brain development...
  47. Nabeshima T, Yamaguchi K, Ishikawa K, Furukawa H, Kameyama T. Potentiation in phencyclidine-induced serotonin-mediated behaviors after intracerebroventricular administration of 5,7-dihydroxytryptamine in rats. J Pharmacol Exp Ther. 1987;243:1139-46 pubmed
    ..These results may indicate that PCP as a 5-HT2 agonist induces head-twitch via 5-HT2 receptors, and that PCP induces head-weaving and turning via 5-HT1 receptors and/or some other mechanisms in rats...
  48. Winter J, Filipink R, Timineri D, Helsley S, Rabin R. The paradox of 5-methoxy-N,N-dimethyltryptamine: an indoleamine hallucinogen that induces stimulus control via 5-HT1A receptors. Pharmacol Biochem Behav. 2000;65:75-82 pubmed
  49. Henry B, Crossman A, Brotchie J. Characterization of enhanced behavioral responses to L-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease. Exp Neurol. 1998;151:334-42 pubmed
  50. Nanry K, Tilson H. The role of 5HT1A receptors in the modulation of the acoustic startle reflex in rats. Psychopharmacology (Berl). 1989;97:507-13 pubmed
    ..These data suggest that 5-HT1a and 5-HT1b receptors play opposite roles in the modulation of the acoustic startle response and that 5-HT plays little, if any, role in the prepulse inhibition of the acoustic startle response...
  51. Halberstadt A, Buell M, Masten V, Risbrough V, Geyer M. Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors. Psychopharmacology (Berl). 2008;201:55-66 pubmed publisher
  52. Kodama T, Mushiake H, Shima K, Hayashi T, Yamamoto M. Slow fluctuations of single unit activities of hippocampal and thalamic neurons in cats. II. Role of serotonin on the stability of neuronal activities. Brain Res. 1989;487:35-44 pubmed
    ..The results show that serotonin in the brain definitely plays a role in stabilizing single neuronal activities...
  53. Minor B, Persson M, Post C, Jonsson G, Archer T. Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine. J Neural Transm. 1988;72:107-20 pubmed
    ..The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia...