SEARCH · PubMed Health

Results for “DOMS”

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 919 records · Page 51Linked to original sources

PubMed1988

Drug discrimination studies with MDMA and amphetamine.

The term entactogen has recently been introduced to describe a new pharmacological class of compounds best represented by 3,4-methylenedioxymethamphetamine, MDMA, and its alpha-ethyl homologue MBDB. The present study was designed to test the similarities of the discriminative stimulus properties produced by MDMA and MBDB, as well as to elaborate further the distinction between entactogens, hallucinogens and stimulants. Two groups of rats were trained to discriminate saline from either racemic MDMA hydrochloride (1.75 mg/kg) or S-(+)-amphetamine sulfate (1.0 mg/kg) in a two-lever drug discrimination task. The (+/-)-MDMA cue completely generalized to S-(+)-MDMA, S-(+)-amphetamine, (+/-)-MDA, S-(+)-MBDB, (+/-)-MBDB, R-(-)-MDMA, and R-(-)-MBDB, but not to LSD or DOM. The S-(+)-amphetamine cue generalized to (+/-)-methamphetamine, but not to racemic MDMA or MBDB, nor to their optical isomers. The S-(+)-isomers of both MDMA and MBDB were more potent than the R-(-)-isomers. The results indicate that MDMA and MBDB may share a component of their discriminative stimulus properties which is different from both stimulants and hallucinogens. Although MDA and MDMA have been shown to be amphetamine-like, the lack of stimulant effects for MBDB suggests that amphetamine-like stimulant activity is not necessary for a compound to share discriminative stimulus properties with MDMA.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1986

Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists.

As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) (20-80 micrograms/kg) was found to have similar effects. Systemic administration of the selective 5-HT2 antagonists LY 53857 (0.02-0.8 mg/kg) and ritanserin (0.1-0.3 mg/kg) completely reversed both actions of the hallucinogens on the LC. In contrast, LY 53857 did not reverse the effects of (+)-amphetamine (0.5 mg/kg) on the spontaneous or sensory-evoked activity of the LC. These results suggest that the common actions of indoleamine and phenethylamine hallucinogens displayed in the LC are mediated via 5-HT2 receptors; however, these receptors appear to be located outside the LC itself.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1984

Some behavioral effects of hallucinogens are mediated by a postsynaptic serotonergic action: evidence from single unit studies in freely moving cats.

Although central serotonergic systems appear to be linked importantly to the mechanism of action of a variety of hallucinogenic drugs, the nature of this interaction has remained unclear. In the present study, the question of whether the critical link is presynaptic or postsynaptic was examined in cats. Behaviorally inactive doses (1.0 mg/kg) of the serotonin receptor antagonists mianserin, ketanserin or metergoline effectively blocked behavior, as measured by the cat limb flick response, elicited by either LSD (50 micrograms/kg) or DOM (250 micrograms/kg) but not that resulting either from lisuride (50 micrograms/kg) or a high dose of apomorphine (4 mg/kg). Pretreatment with 1.0 mg/kg of mianserin, which completely attenuated LSD's behavioral effect, failed to alter LSD-induced depression of mesencephalic serotonergic neuron discharge. These results demonstrate that at least some of the behavioral effects of LSD can be blocked by pharmacological antagonism of postsynaptic serotonin receptors which leaves LSD's presynaptic effect unaffected. Thus, the behavioral, and possibly psychoactive, effects of hallucinogens appear to be attributable to an action at 5HT2 receptors, presumably located postsynaptically.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1986

Phenethylamine hallucinogens in the locus coeruleus: potency of action correlates with rank order of 5-HT2 binding affinity.

The rank order of potency for the physiological effects of three phenethylamine hallucinogens in the locus coeruleus (LC) was identical to that previously shown for their 5-HT2 binding affinity [-) DOB greater than DOM greater than ( + )DOB). The behaviorally inactive positional isomer of DOB, SL-7161, did not significantly affect LC unit activity. These results offer insight into structure-activity relationships at 5-HT2 receptors and support earlier findings that the actions of hallucinogens displayed in the LC are mediated via 5-HT2 receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1984

Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents.

The affinities (Ki values) of twenty two psycho-active agents, including LSD, 5-OMe DMT and a series of phenalkylamine derivatives, for cortical 5-HT1 and 5-HT2 binding sites were compared with two measures of behavioral activity. It was found that a significant correlation (r = 0.938) exists between the 5-HT2 binding affinities of these agents and their ED50 values as determined in tests of stimulus generalization using 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) as the training drug. Furthermore, for fifteen of these agents where human data were available, a significant correlation (r = 0.924) also exists between 5-HT2 binding affinities and their human hallucinogenic potencies. The results of this study suggest that the mechanism of action of these agents involves 5-HT2-related events.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1991

Rapid desensitization of central beta-adrenoceptors in rat after subacute treatment with imipramine and calcium entry blockers.

The subcutaneous (s.c.) administration of isoprenaline to rats produced a dose-dependent increase in water drinking which was effectively antagonized by propranolol. This dipsogenic response was significantly inhibited after the intraperitoneal (i.p.) administration of imipramine (15 mg/kg/day), together with either of the following calcium entry blockers, for four days: diltiazem (15 mg/kg/day), verapamil (10 mg/kg/day), nifedipine (10 mg/kg/day) or nicardipine (15 mg/kg/day). Simultaneous injection of the inhibitor of the synthesis of serotonin, p-chlorophenylalanine (200 mg/kg/day, i.p.), did not affect this attenuation of the isoprenaline-induced response. Similarly, the selective 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) or the 5-HT2 receptor antagonist, ketanserin, had no significant effect on the attenuation of isoprenaline-induced drinking behaviour. The inhibition of isoprenaline-induced drinking, was, however, effectively attenuated after treatment of the animals with 6-hydroxydopamine (2.5 micrograms) or clonidine (30 micrograms), injected intracerebroventricularly (i.c.v.). These results indicate that the calcium entry blockers accelerate the desensitization of central beta-adrenoceptors possibly by an action on central adrenoceptors of the rat.

1-Propanol↗

PubMed1986

Discriminative stimulus properties of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT).

Using a two-lever operant procedure, eleven rats were trained to discriminate 0.2 mg/kg of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT) from saline using a variable-interval 15 sec schedule of reinforcement. Once trained, these animals were used in a series of stimulus generalization and stimulus antagonism studies. The 8-OH DPAT-stimulus did not generalize to the 5-HT1B agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) or the 5-HT2 agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), nor could it be attenuated by pre-treatment of the animals with the 5-HT2 antagonist ketanserin. Low doses of spiperone and propranolol were without effect on 8-OH DPAT-appropriate responding, whereas higher doses of these agents resulted in disruption of behavior. Some preliminary structure-activity data were also obtained using several related tetralin analogs. The results of this study demonstrate that the serotonin agonist 8-OH DPAT serves as a discriminative stimulus in rats and that it produces stimulus effects that are probably not 5-HT1B or 5-HT2-mediated.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1988

Variability in the effects of 4-bromo-2,5-dimethoxyamphetamine (DOB) on operant behavior of squirrel monkeys.

Effects of the hallucinogenic drug (+/-)-4-bromo-2,5-dimethoxyamphetamine HCl (DOB, 0.003-0.3 mg/kg) were studied in squirrel monkeys. Only decreases in responding were seen in monkeys studied under 5-min fixed-interval schedules of food presentation. These decreases were blocked by pretreatment with the 5-HT2 antagonist ketanserin (0.1-1.0 mg/kg) and by the non-selective 5-HT antagonists methysergide (0.3 mg/kg) or mianserin (0.1-1.0 mg/kg). Similar decreases in responding and antagonism by 5-HT antagonists were seen at slightly higher doses of DOM HCl (methyl rather than bromo at the 4 position). In contrast to effects under the food schedule, DOB initially produced marked increases in responding of three monkeys studied under schedules of shock avoidance. However, a complex pattern of changes in the effects of DOB emerged when the same doses were given on subsequent occasions. In one monkey, there were graded increases in responding to a peak of just over 200% of control at 0.17 mg/kg when DOB was given in a roughly ascending dose series. However, no increases in responding were observed at any dose when DOB was given on many subsequent occasions (some very widely spaced). A second monkey showed similar increases initially, but responding was suppressed by a formerly rate-increasing dose of DOB (0.1 mg/kg) on two subsequent test days. Later, this dose again produced increases in responding of about the same magnitude as seen initially, but these increases eventually diminished and were no longer observed. In the third monkey, increases in responding after the initial ascending dose series diminished in an irregular manner over the course of successive redeterminations.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1986

Intravenous self-administration of (-)-cathinone and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane in rhesus monkeys.

The reinforcing effects of (-)-cathinone, a pharmacologically active ingredient of khat, and 2-amino-1-(2,5-dimethoxy-4-methyl)phenylpropane ((STP) (DOM)), a hallucinogenic psychotomimetic, were studied by intravenous self-administration experiments in rhesus monkeys. Among the experiments described in this paper, the result of continuous self-administration of (-)-cathinone was briefly reported elsewhere. T. Yanagita, Studies on Cathinones, NIDA Research Monograph 27, Proceedings of 41st Annual Scientific Meeting of the Committee on Problems of Drug Dependence, 1979, pp. 326-327.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed2004

Lysergic acid diethylamide and [-]-2,5-dimethoxy-4-methylamphetamine increase extracellular glutamate in rat prefrontal cortex.

The ability of hallucinogens to increase extracellular glutamate in the prefrontal cortex (PFC) was assessed by in vivo microdialysis. The hallucinogen lysergic acid diethylamide (LSD; 0.1 mg/kg, i.p.) caused a time-dependent increase in PFC glutamate that was blocked by the 5-HT(2A) antagonist M100907 (0.05 mg/kg, i.p.). Similarly, the 5-HT(2A/C) agonist [-]-2,5-dimethoxy-4-methylamphetamine (DOM; 0.6 mg/kg, i.p.), which is a phenethylamine hallucinogen, increased glutamate to 206% above saline-treated controls. When LSD (10 microM) was directly applied to the PFC by reverse dialysis, a rapid increase in PFC glutamate levels was observed. Glutamate levels in the PFC remained elevated after the drug infusion was discontinued. These data provide direct evidence in vivo for the hypothesis that an enhanced release of glutamate is a common mechanism in the action of hallucinogens.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1997

Assessment of the MDA and MDMA optical isomers in a stimulant-hallucinogen discrimination.

The phenylisopropylamine derivatives 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) have been compared to both psychostimulants and hallucinogens in drug discrimination investigations. The stereoisomers of these compounds, in particular those of MDA, appear to produce differential effects. Previous studies have demonstrated that animals trained to discriminate amphetamine from vehicle generalize to the S(+)-isomers but not the R(-)-isomers of MDA and MDMA while animals trained to discriminate LSD from saline generalize to R(-)-MDA and neither isomer of MDMA. However, animals trained to discriminate mescaline from vehicle generalize to both stereoisomers of these phenylisopropylamine derivatives. The present study consisted of two experiments in which a three-choice drug discrimination procedure was employed to compare the stereoisomers of MDA and MDMA to both amphetamine and either mescaline (experiment one) or LSD (experiment two). Sixteen male Sprague-Dawley rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and mescaline (12.5 mg/kg) and eight rats were trained to discriminate S(+)-amphetamine (1.0 mg/kg) and LSD (0.08 mg/kg) from saline in three-choice, food reinforced drug discrimination procedures. Substitution tests were administered with the isomers of MDA and MDMA. In the second experiment, substitution tests were also administered with lower doses of each training compound and with the stimulant cocaine and the hallucinogen 2,5-dimethoxy-4-methylphenylisopropylamine (DOM). In both experiments, all of the isomers produced very few responses on the S(+)-amphetamine lever. In the first experiment, R(-)-MDA and R(-)-MDMA produced nearly complete substitution for mescaline. The results of the second experiment revealed partial substitution for LSD with both isomers of MDMA and S(+)-MDA, and nearly complete substitution with R(-)MDA for LSD. The present findings do not support previous reports that S(+)-MDMA and S(+)-MDMA substitute for S(+)-amphetamine. The three-lever drug discrimination procedure may provide a more sensitive behavioral assay in which to examine the discriminative stimulus effects of drugs with compound stimulus properties.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1980

Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear substituted 2-amino-1-phenylbutanes.

A series of 2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes (Table V) was prepared as analogues of (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane (1a). 1-(2,5-Dimethoxyphenyl)-2-(N-phthalimido)butane (7) was utilized as a synthetic intermediate common to many of the target compounds. Animal data are presented indicating that most of these analogues have low hallucinogenic potential. Selected compounds were compared with 1a in an avoidance-response acquisition model which differentiates between 1a and the human hallucinogens DOM (2a) and DOET (2b). Structure-activity relationships of these analogues are discussed.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1977

In vitro O-demethylation of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane.

The possible relationship between metabolism and psychotomimetic activity among the methoxylated 1-phenyl-2-aminopropanes led to our investigation of the in vitro O-demethylation of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (1, DOM, STP). Employing a sensitive and highly selective stable isotope dilution assay, we observed that rabbit liver homogenates biotransform the amine 1 to its 2-O-demethyl, 5-O-demethyl, and bis (O-demethyl) metabolite metabolites. Both monophenolic metabolites are enriched in their S enantiomers. The bis(O-demethyl) metabolite has structural, chemical, and electrochemical similarites to the sympatholytic agent "6-hydroxydopamine". The possible significance of metabolic O-demethylation in terms of the psychotomimetic properties of amine 1 is discussed.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1977

Monomethylthio analogues of 1-(2,4,5-trimethoxyphenyl)-2-aminopropane.

Regiospecific syntheses of the three monomethylthio analogues of 1-(2,4,5-trimethoxyphenyl)-2-aminopropane are described. The three isomeric amines were evaluated for potential psychotomimetic potency using the rabbit hyperthermia assay. Enantiomeric compositions and time-concentration curves in rat brains were determined following intraperitoneal administration of each compound. The biological data are contrasted with the corresponding results obtained with the potent human psychotogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM).

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1984

Substituent branching in phenethylamine-type hallucinogens: a comparison of 1-[2,5-dimethoxy-4-(2-butyl)phenyl]-2-aminopropane and 1-[2,5-dimethoxy-4-(2-methylpropyl)phenyl]-2-aminopropane.

Two novel hallucinogen analogues related to 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM, STP) were synthesized and evaluated in the two-lever drug discrimination paradigm by using 0.08 mg/kg of LSD as the training drug stimulus. The two compounds differ from each other only with respect to the point of branching in the 4-alkyl group. However, pharmacological evaluation revealed a clear difference in difference in potency and degree of LSD generalization for the two isomers. Branching adjacent to the ring, as in the 4-(2-butyl) analogue, may provide steric interference to the formation of the drug-receptor complex, while branching one methylene unit removed from the ring, as in the 4-(2-methylpropyl) analogue, poses less of a steric problem for the drug-receptor interaction. This is consistent with the idea that formation of a charge-transfer complex between the hallucinogen molecule and the receptor may be one of the features of this drug-receptor interaction.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed1999

Determinants of CD4 independence for a human immunodeficiency virus type 1 variant map outside regions required for coreceptor specificity.

Although infection by human immunodeficiency virus (HIV) typically requires an interaction between the viral envelope glycoprotein (Env), CD4, and a chemokine receptor, CD4-independent isolates of HIV and simian immunodeficiency virus have been described. The structural basis and underlying mechanisms for this phenotype are unknown. We have derived a variant of HIV-1/IIIB, termed IIIBx, that acquired the ability to utilize CXCR4 without CD4. This virus infected CD4-negative T and B cells and fused with murine 3T3 cells that expressed human CXCR4 alone. A functional IIIBx env clone exhibited several mutations compared to the CD4-dependent HXBc2 env, including the striking loss of five glycosylation sites. By constructing env chimeras with HXBc2, the determinants for CD4 independence were shown to map outside the V1/V2 and V3 hypervariable loops, which determine chemokine receptor specificity, and at least partly within an area on the gp120 core that has been implicated in forming a conserved chemokine receptor binding site. We also identified a point mutation in the C4 domain that could render the IIIBx env clone completely CD4 dependent. Mutations in the transmembrane protein (TM) were also required for CD4 independence. Remarkably, when the V3 loop of a CCR5-tropic Env was substituted for the IIIBx Env, the resulting chimera was found to utilize CCR5 but remained CD4 independent. These findings show that Env determinants for chemokine receptor specificity are distinct from those that mediate CD4-independent use of that receptor for cell fusion and provide functional evidence for multiple steps in the interaction of Env with chemokine receptors. Combined with our observation that the conserved chemokine receptor binding site on gp120 is more exposed on the IIIBx gp120 (T. L. Hoffman, C. C. LaBranche, W. Zhang, G. Canziani, J. Robinson, I. Chaiken, J. A. Hoxie, and R. W. Doms, Proc. Natl. Acad. Sci. USA 96:6359-6364, 1999), the findings from this study suggest novel approaches to derive and design Envs with exposed chemokine receptor binding sites for vaccine purposes.

Amino Acid Sequence↗

PubMed1983

Effect of zotepine on head-twitch induced by L-5-hydroxytryptophan, mescaline and 2,5-dimethoxy-4-methylamphetamine in mice and rats.

The effect of zotepine, a new neuroleptic, on head-twitch induced by L-5-hydroxytryptophan (L-5HTP), mescaline and 2,5-dimethoxy-4-methylamphetamine (DOM) in mice and rats was compared with that of known neuroleptics and the serotonin receptor blocker cyproheptadine. Among the neuroleptics tested, zotepine and haloperidol produced potent inhibitory effects on head-twitch induced by these three drugs. The results indicate that zotepine has a potent anti-hallucinogenic effect.

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↗