PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “DOM 2,5-Dimethoxy-4-Methylamphetamine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1992

Specific esponse to 5-HT2 agonists by arterioles linked to Meth A tumors in mice.

Using intravital microscopy, we compared the responses to serotonin [5-hydroxytryptamine (5-HT)] and to a specific 5-HT2 agonist [1-(2,5-dimethoxy-4-bromo-phenyl)-2-aminopropane (DOB)] by normal arterioles and by the host-modified arterioles feeding a Meth A tumor implanted into the flank of female BALB/c mice. Topical and intravenous administration of 5-HT (10(-6) to 10(-4) M and 0.01-10 micrograms) or DOB (5 x 10(-7) to 5 x 10(-5) M and 0.01-10 micrograms) induced arteriolar constriction, which was far more pronounced for the arterioles feeding the tumor. This larger degree of vasoconstriction in tumor-feeding vs. normal arterioles was not found with norepinephrine. We also compared tumor growth and the mouse life span in three groups of mice, which were given 1 mg of serotonin or 0.74 mg DOB or saline solution. 5-HT or DOB both reduced tumor growth drastically compared with the controls (P less than 0.001), and survival rates were significantly higher in the 5-HT or DOB-treated groups (P less than 0.001). We conclude that 5-HT2-serotoninergic agonists are of particular pharmacological interest, since their vasoconstrictive action on the microvasculature feeding the tumors is much greater than in normal tissue and may interfere with tumor growth.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1976

Drug flashbacks. II. Some additional findings.

A subsample was drawn from an earlier collection of data in order to answer a number of questions related to "acid" (LSD, STP) flashbacks. Acid users who reported flashbacks also reported significantly more marijuana use than those who did not; the two groups did not differ on use of other drugs, including acid. Simple correlations and multiple regression analyses both showed extent of marijuana use to be the only drug variable significantly related to acid flashbacks. No optimal combination of marijuana and acid improved flashback prediction. Among acid users, correlations between amounts of use for various drugs were high and significant, excepting only the marijuana-acid correlation.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1976

Discriminative response control by psychomotor stimulants.

Psychomotor stimulants are capable of controlling discriminative responding in rats. Evidence suggests that response control is central, of a fairly specific nature, and dependent on intact dopaminergic functions.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1975

Metabolic O-demethylation of the psychotomimetic amine 1-(2, 5-dimetroxy-4-methylphenyl)-2-aminopropane.

In an effort to more fully characterize the metabolic fate of the psychotomimetic amine (1-(2, 5-dimethoxy-4-methylpheny.)-2-aminopropane (DOM, STP), the formation of the two possible monophenols and the p-hydroquinone metabolites of the parent drug by 10,000 X g supernatent fractions of rabbit liver homogenates has been investigated. All three metabolites have been fully characterized and quantitatively estimated by chemical ionization mass spectrometry with the aid of deuterium enriched compounds. The stereochemical course of the mono-O-demethylation reactions has been shown to proceed with enantiomeric enrichment of the S-aminophenols. The mechanistic implications concerning the mode of action of the parent drug and metabolic O-demethylation are discussed.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1992

Fourier transform infrared/Raman differentiation and characterization of cis- and trans-2,5-dimethoxy-4,beta-dimethyl-beta-nitrostyrenes: precursors to the street drug STP.

Fourier transform Raman and infrared spectra of pure cis(Z)- and trans(E)-2,5-dimethoxy-4,beta-dimethyl-beta-nitrostyrene (precursors of the psychotomimetic street drug STP or DOM) were recorded in the solid state. The spectra show characteristic features of the ethylene moiety and of the aryl and nitro substituents which permit ready differentiation and identification of these isomers. A very strong Raman line at 1670 cm-1 from the cis isomer for the C=C stretching mode, in comparison with a strong Raman line at 1641 cm-1 for the trans isomer, affords primary differentiation of these substances. A second characteristic, of both the Raman and infrared (IR) spectra, is that the frequency of the strong symmetric nitro (NO2) stretching band is about 40 cm-1 higher in the cis (1346 cm-1) than the trans isomer (1301 cm-1). All major IR and Raman bands are reported and given vibrational assignments.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMedDate not supplied

5-HT2 receptor-stimulated calcium influx in ovine uterine artery in late pregnancy.

The effects of 5-hydroxytryptamine (5-HT) and 2,5-dimethoxy-4-methyl-amphetamine (DOM) on the Ca2+ influx in the ovine uterine artery in late pregnancy have been studied by measuring 45Ca2+ uptake. Both 5-HT and DOM (2.5 x 10(-8) M to 2.5 x 10(-5) M) induced concentration-dependent rises in 45Ca2+ uptake in the ovine uterine artery, from a basal level of 30.5 +/- 3.5 muMoles/kg wet tissue to peak levels of 91.1 +/- 9.2 and 84.2 +/- 8.1 muMoles/kg wet tissue, respectively. The Ca2+ influx evoked by 5-HT and DOM was inhibited by ketanserin in a concentration-dependent manner. Methiothepin (2.5 x 10(-7) M) also inhibited 5-HT-induced (2.5 x 10(-6) M) Ca2+ influx by 86%. No antagonism was found with 2.5 x 10(-6) M of 3-tropanyl-3,5-dichlorobenzoate (MDL 72222). The contraction elicited to 5-HT (10(-6) M) and DOM (10(-6) M) was blocked by D600 (10(-6) M) which also blocked the contraction produced to KCl (9 x 10(-2) M). Amrinone (10(-5) M) had no inhibitory effect on these contractions. In accord with the results of the contraction study, D600 (2.5 x 10(-6) M) blocked the Ca2+ influx stimulated by 5-HT (2.5 x 10(-6) M) and amrinone (2.5 x 10(-5) M) failed to inhibit 5-HT-induced Ca2+ influx. Nifedipine (2.5 x 10(-6) M) did not antagonize the influx of Ca2+ induced by 5-HT. Sodium nitroprusside inhibited the 5-HT-induced Ca2+ influx, indicating that at least part of its inhibitory effect on the vasoconstriction evolved by 5-HT is due to the inhibition of the influx of Ca2+.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1991

The 5-hydroxytryptamine2 agonist, (+-)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane stimulates the hypothalamic-pituitary-adrenal (HPA) axis. I. Acute effects on HPA axis activity and corticotropin-releasing factor-containing neurons in the rat brain.

Corticotropin-releasing factor (CRF) is the major physiological regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary. In vivo and in vitro studies have suggested that hypothalamic CRF secretion is under stimulatory serotonergic control, although the receptor subtype(s) responsible have not been definitely determined. The acute effects of the 5-hydroxytryptamine2 agonist, (+-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB), were examined on a number of biochemical indices of hypothalamic-pituitary-adrenal axis activity in vivo. DOB increased plasma ACTH and corticosterone concentrations at doses greater than 0.1 mg/kg. This effect is dose-dependent. Peak effects occurred 30 min postinjection and returned to basal levels by 4 hr after DOB injection. These effects of DOB are hypothesized to be mediated by the release of hypothalamic CRF because pretreatment with the CRF receptor antagonist (alpha-helical CRF9-41) significantly attenuated the ACTH response to DOB. Median eminence CRF content was also decreased following DOB administration in the presence of the protein synthesis inhibitor, cycloheximide (200 mg/kg i.p.), suggestive of release of CRF from median eminence terminals as a result of DOB activation of CRF neurons. DOB administration was without effect on brain CRF concentrations in all of the 12 extrahypothalamic brain regions studied 60 min after injection. These results, taken together, support a stimulatory role for 5-hydroxytryptamine2 receptors on hypothalamic CRF secretion.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1991

The 5-hydroxytryptamine2 agonist, (+-)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane stimulates the hypothalamic-pituitary-adrenal (HPA) axis. II. Biochemical and physiological evidence for the development of tolerance after chronic administration.

In order to investigate the long term effects of the 5-hydroxytryptamine2 (5-HT2) receptor agonist, (+-)-1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB), on hypothalamic-pituitary-adrenal (HPA) axis activity, DOB (0.35 mg/kg/day) was administered via osmotic minipumps to rats for 7 days at which time plasma adrenocorticotrophic hormone (ACTH), corticosterone and regional brain corticotropin-releasing factor (CRF) concentrations were measured. In addition, anterior pituitary CRF and frontal cortical 5-HT2 receptor binding was measured. Seven-day infusion of DOB resulted in tolerance to the stimulatory actions of the drug on the HPA axis as evidenced by the return of plasma ACTH and corticosterone concentrations to base-line values. Moreover, rats treated chronically with DOB exhibited decreased numbers of both anterior pituitary CRF and cortical and hypothalamic 5-HT2 receptor. These receptor changes were physiologically significant as challenges doses of DOB or CRF resulted in blunted ACTH responses. Chronic DOB infusion was without effect on CRF concentrations in all hypothalamic and extrahypothalamic brain regions studied. A series of time course experiments revealed that DOB-induced increases in plasma corticosterone returned to base-line by 2-days postimplantation. This effect was apparently associated with down-regulation of the 5-HT2 receptor because high-affinity cortical [3H]DOB and hypothalamic (+-)-[125I]-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane binding were decreased at this time as well. Although median eminence CRF content was unchanged at all time points, anterior pituitary CRF receptor binding was significantly decreased 7 days postimplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1990

Electrophysiological characterization of 5-hydroxytryptamine2 receptors in the rat medial prefrontal cortex.

The aim of the present study was to characterize 5-hydroxytryptamine2 (5-HT2) receptors in the rat medial prefrontal cortex (mPFc) by single cell recording and microiontophoretic techniques. This was accomplished using 5-HT2 receptor agonists 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane [(+/-)-DOI] and 1-[2,5-dimethoxy-4-bromophenyl]-2-aminopropane [(+/-)-DOB]. DOI ejected at a low current (0.5 nA) potentiates glutamate (GLU)-induced activation of mPFc neurons and this effect is blocked by spiperone. At higher currents. DOI invariably inhibits GLU-induced neuronal activity. The microiontophoretic ejection of both DOI and DOB predominantly inhibits spontaneously active mPFc cells. The inhibitory action of DOI on spontaneously active cells is dose-dependent and is blocked by putative 5-HT2 receptor antagonists, with a rank order of potency as follows: ritanserin greater than metergoline approximately LY-53857 greater than spiperone greater than mesulergine greater than mianserin approximately ketanserin. Interestingly, ketanserin and mianserin only weakly block the effect of DOI. The suppressant action of DOI is probably not related to its interaction with 5-HT10 sites as spiperone, which has low affinity for these sites, potently blocks the effect of DOI. The suppressant effect of DOI is not blocked by other receptor antagonists such as BRL-43694 (5-HT3), (+/-)-pindolol (5HT 1a,1b, beta adrenergic, beta), prazosin (adrenergic1, alpha-1), pyrilamine (histamine1, H1), l-sulpiride (dopamine2, D2) or SR 95103 (gamma-aminobutyric acid, GABAA). Overall our results indicate that DOI predominantly inhibits mPFc cells in a direct manner and this effect is mediated by 5-HT2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1990

Characterization of serotonergic receptors mediating contraction of ovine umbilical artery.

Responses to serotonergic agonists were studied in isolated umbilical arteries obtained from fetal lambs within 2 weeks of term. The order of potency of the agonists was determined to be 2,5-dimethoxy-4-methyl-amphetamine (DOM) greater than 5-hydroxytryptamine (5-HT) greater than alpha-methyl-5-HT greater than 1-(3-chlorophenyl) piperazine = m-trifluoromethyl-phenylpiperazine greater than 8-hydroxy-dipropylaminotetralin greater than 2-methyl-5-HT greater than 1-(2-methoxyphenyl) piperazine. Variations in the sensitivity and potency of the agonists results primarily from the variation in the affinity for the 5-HT2 receptor and less so in the efficacy, alpha-Methyl-5-HT was a full agonist compared to 5-HT. The others were partial agonists. The mean KA values for 5-HT and DOM were 4.71 +/- 0.62 x 10(-7) and 0.36 +/- 0.04 x 10(-7) M, respectively. Contractions to 5-HT and DOM were antagonized by ketanserin with pA2 values being 9.4 and 9.1, respectively, suggesting that they act on the same receptor and that their responses are mediated by 5-HT2 receptors. Contractile responses to 8-hydroxy-dipropylaminotetralin, 2-methyl-5-HT and the phenylpiperazines [m-trifluoromethyl-phenylpiperazine and 1-(3-chlorophenyl) piperazine] were also blocked by ketanserin (10(-8) M), indicating that contractions produced by these agonists were mediated by 5-HT2 receptors. No antagonism by MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) of responses to 5-HT indicates that 5-HT3 receptors are not present in this tissue.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1990

[3H]-DOB(4-bromo-2,5-dimethoxyphenylisopropylamine) and [3H] ketanserin label two affinity states of the cloned human 5-hydroxytryptamine2 receptor.

The binding properties of the 5-hydroxytryptamine2 (5-HT2) receptor have been the subject of much interest and debate in recent years. The hallucinogenic amphetamine derivative 4-bromo-2,5-dimethoxyphenylisopropylamine (DOB) has been shown to bind to a small number of binding sites with properties very similar to [3H]ketanserin-labeled 5-HT2 receptors, but with much higher agonist affinities. Some researchers have interpreted this as evidence for the existence of a new subtype of 5-HT2 receptor (termed 5-HT2A), whereas others have interpreted these data as indicative of agonist high affinity and agonist low affinity states for the 5-HT2 receptor. In this investigation, a cDNA clone encoding the serotonin 5-HT2 receptor was transiently transfected into monkey kidney Cos-7 cells and stably transfected into mouse fibroblast L-M(TK-) cells. In both systems, expression of this single serotonin receptor cDNA led to the appearance of both [3H]DOB and [3H]ketanserin binding sites with properties that matched their binding characteristics in mammalian brain homogenates. Addition of guanosine 5'-(beta, gamma-imido) triphosphate [Gpp(NH)p] to this system caused a rightward shift and steepening of agonist competition curves for [3H] ketanserin binding, converting a two-site binding curve to a single low affinity binding state. Gpp(NH)p addition also caused a 50% decrease in the number of high affinity [3H]DOB binding sites, with no change in the dissociation constant of the remaining high affinity states. These data on a single human 5-HT2 receptor cDNA expressed in two different transfection host cells indicate that [3H]DOB and [3H]ketanserin binding reside on the same gene product, apparently interacting with agonist and antagonist conformations of a single human 5-HT2 receptor protein. These observations are consistent with the classical view of interconvertible agonist affinity states of GTP-binding protein-coupled receptors and strongly support the "two state" over the "two receptor" model for DOB binding to the 5-HT2 receptor.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗