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At least 235 records · Page 13Linked to original sources
PubMed2001

Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method.

A method for the solid-phase extraction (SPE) and liquid chromatographic-atmospheric pressure chemical ionization-mass spectrometric-mass spectrometric-isotope dilution (LC-APcI-MS-MS-ID) analysis of the indole hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy DMT (or O-methyl bufotenin, OMB) from rat brain tissue is reported. Rats were administered DMT or OMB by the intraperitoneal route at a dose of 5 mg/kg and sacrificed 15 min post treatment. Brains were dissected into discrete areas and analyzed by the methods described as a demonstration of the procedure's applicability. The synthesis and use of two new deuterated internal standards for these purposes are also reported.

Animals↗
PubMed1988

The effects of serotonin agonists and antagonists on the response properties of complex ganglion cells in the rabbit's retina.

Selective agonists and antagonists were employed to determine the role of indoleaminergic amacrine cells in the generation of the light-evoked responses and spontaneous activity of direction and orientation selective cells. Perfusion with 5-HT2 antagonists reduced the spontaneous activity and both the leading and trailing edge responses of ON/OFF direction selective cells. 5-HT1a agonists had a similar effect on this class of cell, namely, a reduction of light-evoked and spontaneous activity. Results from ON-center and OFF-center orientation selective cells were consistent with those obtained from direction selective cells in that no disruption of direction or orientation selectivity was observed during perfusion of these drugs. These data suggest that the indoleaminergic cells are not directly involved in the generation of the trigger features of complex ganglion cells, but may be facilitating synaptic transmission in the inner retina. This function is discussed relative to the connectivity of the rod bipolar cells and the putative indoleaminergic amacrine cells. The similarity of the effects of 5-HT1a agonists and 5-HT2 antagonists supports the hypothesis, developed during our prior studies of brisk ganglion cells, that these two receptor classes mediate antagonistic processes in the target neurons.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

2-Substituted tryptamines: agents with selectivity for 5-HT(6) serotonin receptors.

Several 2-alkyl-5-methoxytryptamine analogues were designed and prepared as potential 5-HT(6) serotonin agonists. It was found that 5-HT(6) receptors accommodate small alkyl substituents at the indole 2-position and that the resulting compounds can bind with affinities comparable to that of serotonin. In particular, 2-ethyl-5-methoxy-N, N-dimethyltryptamine (8) binds with high affinity at human 5-HT(6) receptors (K(i) = 16 nM) relative to 5-HT (K(i) = 75 nM) and was a full agonist, at least as potent (8: K(act) = 3.6 nM) as serotonin (K(act) = 5.0 nM), in activating adenylate cyclase. Compound 8 displays modest affinity for several other populations of 5-HT receptors, notably h5-HT(1A) (K(i) = 170 nM), h5-HT(1D) (K(i) = 290 nM), and h5-HT(7) (K(i) = 300 nM) receptors, but is otherwise quite selective. Compound 8 represents the first and most selective 5-HT(6) agonist reported to date. Replacing the 2-ethyl substituent with a phenyl group results in a compound that retains 5-HT(6) receptor affinity (i.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.

Adenylyl Cyclases↗
PubMed1986

Differential interactions of "prosexual" drugs with 5-hydroxytryptamine1A and alpha 2-adrenergic receptors.

Radioligand binding studies were used to analyze the interactions of six "prosexual" drugs with 5-hydroxytryptamine1A (5-HT1A) and alpha 2-adrenergic receptors in rat brain membranes. Three drugs that facilitate seminal emissions and/or ejaculations [8-hydroxy-2-n-propylaminotetralin (8-OH-DPAT), 5-methoxy-dimethyltryptamine, and RDS-127] are potent and selective inhibitors of [3H]8-OH-DPAT binding to 5-HT1A receptors. By contrast, three drugs with primary sexual arousal effects (yohimbine, imiloxan, and idazoxan), are potent agents at alpha 2-adrenergic receptors labeled by [3H]yohimbine. These data suggest that radioligand binding analysis of prosexual agents may elucidate the pathophysiology of sexual behavior.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Characterisation of human 5-hydroxytryptamine2A and 5-hydroxytryptamine2C receptors expressed in the human neuroblastoma cell line SH-SY5Y: comparative stimulation by hallucinogenic drugs.

Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT2C receptor (pEC50 = 7.80 +/- 0.06) compared with the 5-HT2A receptor (pEC50 = 7.30 +/- 0.08). Activation of the 5-HT2A receptor caused a transient fourfold increase in intracellular Ca2+ concentration. Whole-cell recordings of cells clamped at -50 mV demonstrated a small inward current (2 pA) in response to 10 microM 5-HT for both receptors. There were no differences in potency or efficacy of phosphoinositide hydrolysis among four hallucinogenic [d-lysergic acid diethylamide (LSD), 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI), 5-methoxy-N,N-dimethyltryptamine, and mescaline] and three nonhallucinogenic drugs (m-chlorophenylpiperazine, quipazine, and ergotamine). Comparison of equipotent doses producing 20% of the maximal response induced by 5-HT revealed selective activation of the 5-HT2A receptor by LSD and to a lesser degree by DOI, mescaline, and ergotamine. Quipazine and 5-methoxy-N,N-dimethyltryptamine were relatively nonselective, whereas m-chlorophenylpiperazine selectively activated the 5-HT2C receptor. It is unlikely therefore that hallucinosis is mediated primarily by activity at the 5-HT2C receptor, whereas activity at the 5-HT2A receptor may represent an important but not unique mechanism associated with hallucinogenic drug action.

Adrenergic alpha-Agonists↗
PubMed2001

Determination of potentially hallucinogenic N-dimethylated indoleamines in human urine by HPLC/ESI-MS-MS.

A new method for the determination of N,N-dimethyl-5-hydroxytryptamine (bufotenine), N,N-dimethyltryptamine (DMT)*, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), and N-methyltryptamine (NMT) was developed using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Identification of the analytes is based on liquid chromatographic retention times of analytes and two fragment ions produced by a triple quadrupole mass spectrometer. Quantification is based on electrospray ionization (ESI), and multiple reaction monitoring (MRM) was also utilized for getting better selectivity. The analytes and internal standard were separated from the urine matrix by solid-phase extraction (SPE). The method was applied for the determination of these compounds in urine samples of patients from surgical, medical and psychiatric wards. Of the dimethylated amines, only bufotenine was found in significant amounts (up to 34 microg/L). In keeping with our earlier results, the bufotenine excretion of psychiatric patients was found to be higher than that of the somatic patients. Method, procedure, considerations, statistical evaluations and urine sample spectra are presented.

Bufotenin↗
PubMedDate not supplied

Pharmepéna-Psychonautics: Human intranasal, sublingual and oral pharmacology of 5-methoxy-N,N-dimethyl-tryptamine.

Summarized are psychonautic bioassays (human self-experiments) of pharmepéna--crystalline 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; O-Me-bufotenine), at times combined with crystalline beta-carbolines (harmaline or harmine). These substances were administered via intranasal, sublingual and oral routes, by way of pharmacological modeling of diverse South American shamanic inebriants (principally the snuffs epéna/nyakwana, prepared from barks of diverse species of Virola.) Intranasal, sublingual and oral psychoactivity of 5-MeO-DMT, and the 1967 Holmstedt-Lindgren hypothesis of the paricá-effect--intranasal potentiation of tryptamines by concomitant administration of monoamine-oxidase-inhibiting (MAOI) beta-carbolines from stems of Banisteriopsis caapi admixed with the snuffs--have been confirmed by some 17 psychonautic bioassays. Salient phytochemical and psychonautic literature is reviewed.

Administration, Intranasal↗
PubMedDate not supplied

A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation.

A case of a 25-year-old white male who was found dead the morning after consuming herbal extracts containing beta-carbolines and hallucinogenic tryptamines is presented. No anatomic cause of death was found at autopsy. Toxicologic analysis of the heart blood identified N,N-dimethyltryptamine (0.02 mg/L), 5-methoxy-N,N-dimethyltryptamine (1.88 mg/L), tetrahydroharmine (0.38 mg/L), harmaline (0.07 mg/L), and harmine (0.17 mg/L). All substances were extracted by a single-step n-butyl chloride extraction following alkalinization with borate buffer. Detection and quantitation was performed using liquid chromatography-electrospray mass spectrometry. The medical examiner ruled that the cause of death was hallucinogenic amine intoxication, and the manner of death was undetermined.

Adult↗
PubMed1993

Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys.

A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA/benserazide 50/12.5 mg/kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. 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.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1982

5-hydroxytryptamine stimulates [3H]dopamine release from the fish retina.

Serotonin (5-hydroxytryptamine, 5-HT; 0.5 micro M and above) stimulated the release of [3H]dopamine ([3H]DA) from particulate fractions of the carp (Cyprinus carpio) retina. The 5-HT effect was dose- and Ca2+-dependent, and was structurally specific. A similar response was not elicited by the other indoles (5,6-dihydroxytryptamine, 5,7-dihydroxytryptamine, 5-hydroxytryptophan, or 5-hydroxyindoleacetic acid) examined. An increase in [3H]DA release was elicited by addition of 5-HT agonists (5-methoxytryptamine, 5-methoxy-N,N-dimethyltryptamine, and tryptamine), but not antagonized by three 5-HT antagonists (metergolin, methysergide, and spiperone). Either DA alone or noradrenaline (0.5 mM) produced a large increase in [3H]DA release from the particulate fractions, but this action was Ca2+-independent. Further, no significant release of [3H] gamma-aminobutyric acid could be evoked by 5-HT (0.5 mM) under similar experimental conditions. Taken together, the present data suggest that 5-HT stimulates [3H]DA release from the fish retina through a specific receptor-mediated mechanism on dopaminergic terminals, but not through an exchange or nonspecific phenomenon.

5-Methoxytryptamine↗
PubMed1985

Indoleamine-sensitive adenylate cyclase in rabbit retina: characterization and distribution.

Previous histological, electrophysiological, and biochemical reports have addressed the hypothesis that serotonin functions as a neurotransmitter in mammalian retinas. We have tested the effect on the levels of cyclic AMP of the application of exogenous serotonin, 5-methoxytryptamine, melatonin, and 5-methoxydimethyl-tryptamine to isolated, incubated rabbit retinas. All indoleamines tested significantly elevated intracellular levels of cyclic AMP in both light- and dark-adapted, incubated, intact retinas, provided a phosphodiesterase inhibitor was present. In homogenates of rabbit retina, all indoleamines tested also markedly increased adenylate cyclase activity over basal levels. Maximal activity was observed with 50 microM indoleamine; addition of GTP augmented this increase. The increase in enzyme activity persisted in the presence of known antagonists of dopamine and serotonin 5-HT2-receptors, but was blocked by the mixed 5-HT1, 5-HT2-antagonist lysergic acid diethylamide. The retinal locations of this response have also been identified using layer microdissection techniques on freeze-dried samples obtained from rabbit eyecups suprafused with indoleamine plus phosphodiesterase inhibitor. Cyclic AMP levels were measured in discrete retinal layers of both light- and dark-adapted suprafused eyecups, and increased levels were observed primarily in the inner and outer plexiform layers, which contain the synapses of the retinal neurons.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Serotonin agonists reduce dopamine synthesis in the striatum only when the impulse flow of nigro-striatal neurons is intact.

The effects of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT) and m-chlorophenylpiperazine (CPP), two 5-hydroxytryptamine (5-HT, serotonin) agonists, on the accumulation of 3,4-dihydroxyphenylalanine (DOPA] were studied in the striatum of rats treated with gamma-butyrolactone (GBL). Unlike 2 mg/kg i.p. apomorphine, neither 5 mg/kg i.p. 5-MeO-DMT nor 2.5 mg/kg i.p. CPP significantly reduced the GBL-induced increase in DOPA accumulation in the striatum. 5-MeO-DMT and CPP significantly reduced DOPA accumulation in animals that had received the aromatic amino acid decarboxylase inhibitor Ro 4-4602 but not GBL. 5-HT (10 micrograms in 0.5 microliter) injected in the substantia nigra, pars compacta, like GBL, significantly increased Ro 4-4602-induced accumulation of DOPA in the striatum. The data indicate that 5-HT agonists can reduce 3,4-dihydroxyphenylethylamine (DA, dopamine) synthesis in the striatum of rats only when the impulse flow of DA neurons is intact. An indirect effect through mechanisms controlling DA synthesis in the striatum, for instance cholinergic and GABA-ergic neurons, is suggested.

4-Butyrolactone↗
PubMed1986

Local cerebral glucose utilisation following indoleamine- and piperazine-containing 5-hydroxytryptamine agonists.

Substances with varying structural components have been shown to have 5-hydroxytryptamine (5-HT)-like properties in the CNS. In this study, putative 5-HT agonists with indoleamine moeities--lysergic acid diethylamide (LSD) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)--and with piperazine moieties--quipazine (Quip) and 6-chloro-2-(1-piperazinyl)pyrazine (6-CPP) were administered to rats. Local cerebral glucose utilisation was measured using the [14C]2-deoxyglucose autoradiographic technique. It was found that in most cerebral structures, these substances produced dose-dependent reductions in glucose utilisation. However, Quip and 6-CPP increased glucose utilisation in specific areas of the diencephalon (e.g., nucleus reuniens) and produced a biphasic effect in some but not all extrapyramidal structures (e.g., ventromedial caudate nucleus). No such increases in local cerebral glucose utilisation were measured following LSD or 5-MeODMT administration. These results indicate that although similarities exist between the effects of indoleamine- and piperazine-containing 5-HT agonists on local cerebral glucose utilisation there are also significant differences in the overall patterns of response produced.

Animals↗
PubMed1986

Stimulation of the serotonin autoreceptor prevents the calcium-calmodulin-dependent increase of serotonin biosynthesis in rat raphe slices.

The role of the serotonin (5-hydroxytryptamine) autoreceptor in the regulation of the activity of tryptophan hydroxylase was investigated in rat raphe slices. The activity of tryptophan hydroxylase was estimated by measuring the accumulation of 5-hydroxytryptophan in the presence of inhibition of aromatic L-amino acid decarboxylase using 3-hydroxy-4-bromobenzyloxy-amine by HPLC with fluorescence detection. Serotonin and its agonists N,N-dimethyl-5-methoxytryptamine and 1-(m-chlorophenyl)-piperazine reduced the formation of 5-hydroxytryptophan to 50-60% at 10(-5) M. The effect of serotonin was reversed by 10(-5) M methiothepin, an antagonist of the serotonin autoreceptor. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5), dose-dependently reduced the basal formation of 5-hydroxytryptophan to 40-50% at 10(-6) and 10(-4) M, respectively. W-7 also reduced the activated formation by A-23187 or dibutyryl cyclic AMP in a dose-dependent manner. W-7 had no effect on 5-hydroxytryptophan formation reduced by serotonin at 10(-5) M. These results suggest that the role of the serotonin autoreceptor was related to the prevention of the calcium-calmodulin-dependent activation of tryptophan hydroxylase.

5-Hydroxytryptophan↗
PubMed1989

In vivo determination of 5-hydroxytryptamine receptor-stimulated phosphoinositide turnover in rat brain.

Phosphoinositide turnover stimulated by 5-hydroxytryptamine (5-HT) receptors in the intact rat brain was studied using an in vivo method. Phosphoinositides in the rat brain were prelabeled with [3H]inositol injected into the lateral cerebral ventricles. The rats were killed by microwave irradiation after 48 h and the contents in the frontal cortex of 3H-inositol phosphates, [3H]inositol-1-monophosphate [( 3H]IP1), [3H]inositol-1,4-bisphosphate [( 3H]IP2), and a mixture of [3H]inositol-1,4,5-trisphosphate and [3H]inositol-1,3,4-trisphosphate [( 3H]IP3) were assayed by HPLC. Lithium treatment (10 mEq/kg, i.p., 2 h before) increased the content of [3H]IP1 and [3H]IP2. 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) and quipazine, 5-HT agonists, significantly increased the amount of 3H-inositol phosphates under lithium pretreatment. The response to 5-MeODMT was inhibited by ritanserin, a 5-HT2 antagonist, but not by (-)-propranolol, a 5-HT1 antagonist. These results suggest that phosphoinositide turnover in the rat frontal cortex in vivo is stimulated by 5-HT2 receptor activation. It is considered that this method will be useful for measurement of 5-HT2 receptor-stimulated phosphoinositide turnover in vivo to examine the in vivo effects of various psychotropic drugs such as antidepressants.

Animals↗
PubMed1983

Calcium-dependency of the pressor responses to selective 5-hydroxytryptamine receptor agonists in pithed rats.

The pressor responses to six selective 5-HT receptor agonists, quipazine, TMFPP, Org 10155, Ru 24969, 5-methoxytryptamine and 5-methoxy-N,N-dimethyltryptamine, were quantified and tested for calcium dependency following i.v. administration to pithed normotensive rats. The pressor responses induced by 5-methoxytryptamine and 5-methoxy-N,N-dimethyltryptamine were not influenced by calcium entry blockade by means of nifedipine. The piperazine derivatives quipazine, TMFPP and Org 10155 were full agonists, but the pressor responses to these agonists were sensitive to calcium entry blockade. 5-Methoxy-N,N-dimethyltryptamine and Ru 24969 were found to be partial agonists. It is submitted as a hypothesis that within the present series of 5-HT receptor agonists, a restricted side chain flexibility will enhance the dependency of their pressor responses to extracellular calcium.

5-Methoxytryptamine↗