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At least 127 records · Page 7Linked to original sources
PubMed1990

High levels of tryptamine accumulation in transgenic tobacco expressing tryptophan decarboxylase.

A full-length complementary DNA clone encoding tryptophan decarboxylase (TDC; EC 4.1.1.28) from Catharanthus roseus (De Luca V, Marineau C, Brisson N [1989] Proc Natl Acad Sci USA 86: 2582-2586) driven by the CaMV 35S promoter was introduced into tobacco (Nicotiana tabacum) to direct the synthesis of the protoalkaloid tryptamine from endogenous tryptophan. Young, fully expanded leaves of CaMV 35S-TDC transformed plants had from four to 45 times greater TDC activity than did controls. Tryptamine accumulated in transgenic plants to levels that were directly proportional to their TDC specific activity. Despite their increased tryptamine content, the growth and development of the CaMV 35S-TDC plants appeared normal with no significant differences in indole-3-acetic acid levels between high tryptamine and control plants. Plants with the highest TDC activity contained more than 1 milligram of tryptamine per gram fresh weight, a 260-fold increase over controls.

Journal Article↗
PubMed1985

5-Carboxamide tryptamine, a compound with high affinity for 5-hydroxytryptamine1 binding sites, dilates arterioles and constricts arteriovenous anastomoses.

The effects of 5-carboxamide tryptamine, which activates non-5-hydroxytryptamine2-'atypical' receptors for 5-hydroxytryptamine (5-HT) in the dog saphenous vein, was studied on the complete distribution of cardiac output and common carotid blood flow in anaesthetized pigs. The drug was infused for 10 min at the rate of 0.025, 0.1 and 0.4 micrograms kg-1 min-1 either intravenously (cardiac output distribution) or intra-arterially (carotid distribution). 5-Carboxamide tryptamine decreased arterial blood pressure due to a reduction of cardiac output. This reduction was confined to its arteriovenous anastomotic component; the component used for the tissue perfusion (nutrient part) in fact increased. Similar changes were observed in the carotid blood flow distribution. Vasodilation was observed in several tissues, but the skin, ears and stomach responded most prominently. The effects of 5-carboxamide tryptamine on the carotid distribution were not significantly modified by cyproheptadine (1 mg kg-1). It is concluded that, like 5-HT, 5-carboxamide tryptamine constricts arteriovenous anastomoses and dilates arterioles by activating non-5-HT2-'atypical' receptors. These 'atypical' 5-HT receptors appear to be of the 5-HT1 type since both 5-carboxamide tryptamine and BEA 1654, a new piperazine derivative, produced similar vascular effects in the carotid bed of the pig and also showed a high and selective affinity for the 5-HT1 binding sites.

Animals↗
PubMed1985

In vitro pigment formation from tryptamine. Role of indole-3-acetaldehyde.

The metabolic significance of indole-3-acetaldehyde in the process of in vitro pigment formation from tryptamine in the presence of guinea-pig liver mitochondria was investigated. Among the four type selective MAO inhibitors used, pargyline and deprenyl appear to be more effective in inhibiting pigment formation from tryptamine than serotonin, while in the presence of clorgyline and Lilly 51641, pigment formation from serotonin was preferentially inhibited. Reducing agents like ascorbic acid, cysteine and glutathione were found to block pigment formation significantly. Also, a reduction of pigment formation was noted in the presence of NADH and ethanol but not in the presence of NAD. It was observed that the amount of indole-3-acetaldehyde produced enzymatically from tryptamine under the present experimental conditions is not sufficient to account for the total amount of pigment formed in the standard incubation mixture and the generation of nascent aldehyde has greater contribution in pigment formation than that supplemented to the system exogenously. It appears that indole-3-acetaldehyde, tryptamine and MAO are associated with the process of pigment formation.

Animals↗
PubMed1986

The oxidation of tryptamine by the two forms of monoamine oxidase in human tissues.

The selective monoamine oxidase inhibitors clorgyline and (-)-deprenyl have been used to determine the activities of monoamine oxidase-A and -B towards tryptamine in several human tissues. The results were compared with those obtained with the A-form-selective substrate 5-hydroxytryptamine, the B-form-selective substrate 2-phenethylamine and the common substrate tyramine. Tryptamine was found to be a substrate for both forms of the enzyme in human liver, kidney cortex and medulla and in seven different brain regions. The Km values of the two forms towards this substrate were similar in all the human tissues examined but the maximum velocities differed. Thus the A-form would contribute approximately 50% of the total monoamine oxidase activity towards this substrate in human cerebral cortex, whereas it would contribute about 60% in kidney cortex and medulla and 75% in liver. These results suggest that both forms of monoamine oxidase would contribute to the metabolism of tryptamine in human tissues and are difficult to reconcile with suggestions that tryptamine excretion may provide a simple index of monoamine oxidase-A inhibition.

Brain↗
PubMed1986

Effect of deuterium substitution on the disposition of intraperitoneal tryptamine.

To determine whether alpha,alpha-dideutero substitution in the side chain of the tryptamine molecule can exert primary isotope effects and enhance its bioavailability, equimolar mixtures of tryptamine (T) and either alpha,alpha-dideutero-tryptamine (alpha,alpha-[2H2]T) or beta,beta-dideutero-tryptamine (beta,beta-[2H2]T) were injected i.p. into rats. The amounts of these amines in the brain, liver and plasma were then measured at various times following the injection, and ratios between the deuterated T and T were computed. The ratio remained close to unity in plasma, but exceeded unity in the liver and brain when alpha,alpha-[2H2]T and T were injected; however, when beta,beta-[2H2]T and T were injected, the ratios were unity in all cases at all times. In the presence of a monoamine oxidase inhibitor, the relative enrichment of alpha,alpha-[2H2]T compared to T was reduced. It is concluded that alpha,alpha-dideutero substitution exerts a primary isotope effect during oxidative deamination so that much more of this amine penetrates into, and persists in, the brain.

Animals↗
PubMed1977

Release of spasmogens from rat isolated lungs by tryptamines.

Tryptamine and 5-hydroxytryptamine (5-HT) infused through the pulmonary circulation of rat isolated lungs released a spasmogen resembling slow reacting substance of anaphylaxis which we have denoted SRS-T and a PGE-like activity. SRS-T was not extractable from Krebs solution by several organic solvents at neutral or acid pH. It is therefore unlike other types of SRS activity. The PGE-like release had a threshold at about 2 microgram/ml of tryptamine or 5-HT and did not increase with increasing doses (up to 10 microgram/ml); this release was abolished by methysergide, BC 105 and BW 501c67 but not by morphine. Comparison of agonist potencies of 5-HT and tryptamine on rat stomach strip and rat pulmonary artery and of antagonist potencies of methysergide, BC 105 and morphine on these tryptamine receptors lead to the conclusion that the release receptors are unlike either of the myotropic receptors. In terms of antagonist specificity the release receptors are closest to those in rat stomach strip.

Animals↗
PubMed1983

Characterization of [3H]tryptamine binding sites in brain.

[3H]Tryptamine binds with high affinity to sites on rat brain membranes. The sites have the characteristics of tryptamine receptor recognition sites. These sites are widely distributed among rat brain regions with the highest density occurring in the cerebral cortex, striatum and hippocampus. The site is also found in human cerebral cortex. The binding site is localized mainly to the synaptosomal fraction. Drug competition studies indicate that the [3H]tryptamine binding site is distinct from serotonin receptors. Drugs that are potent inhibitors of [3H]tryptamine binding include tetrahydro-beta-carboline, quipazine, phenylethylamine, amphetamine, p-chloroamphetamine and methamphetamine.

Animals↗
PubMed1986

Structural relationships in the inhibition of [3H]tryptamine binding to rat brain membranes in vitro by phenylalkylamines.

The ability of various phenylalkylamines to inhibit the binding of [3H]tryptamine to rat frontal/parietal cortical membranes was examined in vitro. Affinity for [3H]tryptamine binding sites improved as the alkyl side chain was extended to include four carbons or when a methoxy group was added at the para position of the ring. One compound, p-methoxyphenylpropylamine (IC50 = 3.6 nM), was as potent as unlabelled tryptamine as a displacing agent. Based on the unique structure-activity relationship obtained, it appears that [3H]tryptamine binding sites do not mediate the actions of phenethylamines on serotonin uptake or release.

Alkylation↗
PubMed1987

Hypothermia induced in mice by intracerebroventricular injection of tryptamine: involvement of the 5-HT1 receptor.

The effect on the body temperature of mice of tryptamine administered by intracerebroventricular (i.c.v.) injection was studied. Tryptamine given i.c.v. produced a significant hypothermia above a dosage of 5 nmol. The hypothermic effect of tryptamine was inhibited by methysergide whereas ketanserin and p-chlorophenylalanine did not affect it. These data demonstrate that the hypothermia induced by tryptamine i.c.v. is produced by direct activation of the 5-HT1 receptor.

Animals↗
PubMed1990

The activation of serotonin receptors by tryptamine induces hyperinsulinemia in mice.

The effects of tryptamine on serum insulin levels were investigated. Tryptamine induced an apparent increase in serum insulin levels in mice. The elevation in insulin elicited by tryptamine was potently antagonized by the 5-HT1 and 5-HT2 receptor antagonist, methysergide, but partially reduced by the 5-HT2 receptor antagonist, ketanserin. However, the 5-HT3 receptor antagonist, ICS 205-930, was without effect. These results indicate that both 5-HT1 and 5-HT2 receptors are involved in the tryptamine-induced increase in insulin levels.

Animals↗
PubMed1986

Temperature-sensitive high affinity [3H]tryptamine binding sites in rat brain.

The influence of prior incubation on [3H]tryptamine binding was investigated in rat brain synaptic plasma membranes. A 55 min preincubation of the membranes at 37 degrees C induced an approx. 2.4-fold increase in the specific binding of [3H]ligand to the subsequently washed preparations and this phenomenon was quite temperature-dependent. On the other hand, the proportion of nonspecific binding sites was significantly decreased by 70% of the original sites within 20 min of the start of preincubation. Pargyline, ascorbic acid, EGTA, metal ions (Ca2+, Mg2+, Na+) and guanine nucleotides, included in the preincubation buffer, were all inactive on the stimulation of [3H]tryptamine binding, while the pretreatment of membranes with glutaraldehyde antagonized the augmentation of this binding. Furthermore, it was revealed that the Scatchard plot of the [3H]tryptamine binding preincubated at 0 degree C conformed to a straight line (KD = 33.1 nM, Bmax = 543 fmoles/mg protein), whereas a curvilinear Scatchard plot was obtained at 37 degrees C preincubation. Nonlinear regression analysis of the latter resulted in apparent KD (nM) & Bmax (fmoles/mg protein) values of 0.45 & 102.7 and 33.7 & 603.4 for the high and low affinity sites, respectively. All these observations lead to the inference that the preincubation-induced increase in [3H]tryptamine binding (i.e., nearly high affinity proportion of sites) may occur as a result of temperature-sensitive interconvertible conformational changes.

Animals↗
PubMed1987

Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites.

In an attempt to define pharmacophoric differences between 5-HT1, 5-HT1A and 5-HT2 recognition sites, a number of rigid analogs were studied and compared to analogous free chain tryptamines. Racemic partial ergolines RU 27849 and RU 28306 showed reduced potency at all 5-HT1 sites, but were at least equipotent to analogous tryptamines at the 5-HT2 site. A nonergoline-like constrained analog of tryptamine was similar in potency to RU 27849 at all 5-HT1 sites, but showed a 4-fold enhancement in potency over RU 27849 and tryptamine at the 5-HT2 site. At all 3 sites, 3-(tetrahydropyridyl) indoles (unless substituted at the indole 2-position) were the most potent rigid analogs studied and represent the most promising class for the development of selective compounds.

Animals↗
PubMed1988

Glutaraldehyde pretreatment blocks temperature-induced high-affinity [3H]tryptamine binding.

The effect of glutaraldehyde (and Azure A) on temperature-sensitive high-affinity [3H]tryptamine binding was investigated in rat brain synaptic plasma membranes. In the 0.01-0.1% concentration range, the glutaraldehyde pretreatment preferentially inhibited only the above-mentioned portion of the binding, whereas the posttreatment of this reagent had no effect. On the other hand, in cases of pretreatment or posttreatment, a concentration of glutaraldehyde as high as 0.1% was inactive on the basal [3H]ligand binding capacity of the membranes (i.e., temperature-independent binding). Furthermore, it was revealed that the Scatchard plot of [3H]tryptamine binding in membranes pretreated with glutaraldehyde (0.05%) conformed to a straight line, as did a similar plot of temperature-independent binding. And, it was interesting to find that the binding parameters (KD and Bmax values) of both samples corresponded closely to each other. On the contrary, in all concentrations, Azure A affected nonspecifically both the temperature-dependent and the independent [3H]tryptamine binding to the same degree, regardless of whether or not there was pretreatment or posttreatment. All these observations clearly demonstrate that an appropriate concentration (0.01-0.1%) of glutaraldehyde pretreatment specifically blocks the temperature-induced allosteric modifications of high-affinity [3H]tryptamine binding sites.

Aldehydes↗
PubMed1986

Indoloquinolizidines, formal derivatives of tetrahydro-beta-carbolines, show selective affinity for benzodiazepine, tryptamine and serotonin binding sites in rat brain.

Beta-carbolines and indoloquinolizidines occur in plants, and some of the former compounds also in mammalian tissues. Many beta-carbolines cause tremor or convulsions, and they are among the most potent known endogenous compounds to bind to benzodiazepine, tryptamine and serotonin binding sites. In this study seven indoloquinolizidines which are formal derivatives of 1,2-disubstituted 1,2,3,4-tetrahydro-beta-carbolines were assayed for their affinity for benzodiazepine, tryptamine and serotonin binding sites in rat brain in vitro. Three of them exhibited significant affinity for tryptamine receptors: Ki values ranged from 0.97 microM upwards. The affinity spectra towards different receptors greatly varied from compound to compound showing selectivity to one or several of the binding sites now studied. These derivatives of beta-carbolines may be useful tools when assessing the physiological functions of the tryptamine and other binding sites.

Animals↗
PubMed1986

Conditioned taste aversion induced by tryptamine: a temporal analysis.

The effects of tryptamine on the induction of a conditioned taste aversion (CTA) to a novel saccharin solution were examined. In a single bottle-repeated injection paradigm, tryptamine (40, 60 and 80 mg/kg, IP) induced a significant CTA. This effect was relatively weak, with only the highest dose tested inducing a progressive decline in saccharin intake across trials. The weak action of tryptamine (40 and 60 mg/kg) was confirmed in a more sensitive CTA paradigm which measured the relative preference for saccharin and water. Results of this experiment also showed that prolonging the duration of action of tryptamine failed to enhance the formation of a CTA. This finding extends previous reports that prolonging the duration of action of a compound does not increase potency in the CTA paradigm, and thus casts doubt on the generality of the duration of action hypothesis.

Animals↗
PubMed2006

Analytical characterisation of the routes by thermolytic decarboxylation from tryptophan to tryptamine using ketone catalysts, resulting in tetrahydro-beta-carboline formation.

N-Alkylated tryptamines have complex psychoactive properties. Routes for clandestine synthesis are described on Internet websites one of which involves the thermolytic decarboxylation of tryptophan to tryptamine as a precursor to psychoactive compounds. High boiling solvents and ketone catalysts have been employed to facilitate the decarboxylation of tryptophan. The present study has revealed that there is formation of tetrahydro-beta-carboline (THBC) derivatives which may originate from reaction with both the solvent and the ketone catalyst. The application of gas chromatography electron- and chemical-ionisation ion trap tandem mass spectrometry (GC-IT-MS-MS), in combination with nuclear magnetic resonance (NMR), led to the isolation and identification of 1,1-disubstituted-tetrahydro-beta-carbolines formed as major impurities in the tryptamine. Confirmation was by synthesis of the THBC derivatives from tryptamine using Pictet-Spengler cyclisation. Under EI-conditions, mass spectral characterisation of the THBCs suggests predominance of alkyl cleavage. These impurities will yield a useful profile for identification of the synthetic pathway and likely reagents employed, particularly a "fingerprint" of the ketone catalyst and an insight into the influence of solvents and catalysts on the formation of by-products.

Carbolines↗
PubMed1978

Reversed-phase high-pressure liquid chromatography of some tryptamine derivatives.

A quantitative reversed-phase high-pressure liquid chromatographic method is described for tryptamine, bufotenine, N-methyltryptamine and N,N-dimethyl tryptamine. All compounds were eluted with base-line separation within 15 min. The method is used to determine the tryptamine level in a leaf extract of Acacia podalyriaefolia A. Cunn. Satisfactory recoveries of tryptamine from plant material, and N,N-dimethyltryptamine from urine were obtained.

Bufotenin↗
PubMed2000

Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines.

A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activation of these compounds at serotonin receptor subtypes. The target compounds were evaluated using in vivo behavioral assays for hallucinogen-like and 5-HT(1A) agonist activity and in vitro radioligand competition assays for their affinity at 5-HT(2A), 5-HT(2C), and 5-HT(1A) receptor sites. Functional activity at the 5-HT(2A) receptor was determined for all compounds. In addition, for some compounds functional activity was determined at the 5-HT(1A) receptor. Hallucinogen-like activity, evaluated in the two-lever drug discrimination paradigm using LSD-trained rats, was attenuated or abolished for all of the fluorinated analogues. One of the tryptamines, 4-fluoro-5-methoxy-DMT (6), displayed high 5-HT(1A) agonist activity, with potency greater than that of the 5-HT(1A) agonist 8-OH-DPAT. The ED(50) of 6 in the two-lever drug discrimination paradigm using rats trained to discriminate the 5-HT(1A) agonist LY293284 was 0.17 micromol/kg, and the K(i) at [(3)H]8-OH-DPAT-labeled 5-HT(1A) receptors was 0.23 nM. The results indicate that fluorination of hallucinogenic tryptamines generally has little effect on 5-HT(2A/2C) receptor affinity or intrinsic activity. Affinity at the 5-HT(1A) receptor was reduced, however, in all but one example, and all of the compounds tested were full agonists but with reduced functional potency at this serotonin receptor subtype. The one notable exception was 4-fluoro-5-methoxy-DMT (6), which had markedly enhanced 5-HT(1A) receptor affinity and functional potency. Although it is generally considered that hallucinogenic activity results from 5-HT(2A) receptor activation, the present results suggest a possible role for involvement of the 5-HT(1A) receptor with tryptamines.

3T3 Cells↗