MDA: an agent that produces stimulus effects similar to those of 3,4-DMA, LSD and cocaine.
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3,4-Methylenedioxyamphetamine↗
Biomedical subjects
R Young
Publications and source records attributed to R Young.
MDA: a psychoactive agent with dual stimulus effects.
Rats were trained to discriminate injections of either (+)-amphetamine (1.0 mg/kg) or racemic MDA (1.5 mg/kg) from saline in a two-lever drug discrimination task. After stable discrimination performances (greater than 85%) were attained in each group, stimulus generalization studies were conducted. The amphetamine-stimulus generalized to MDA, but not to the hallucinogenic agent DOM; the MDA-stimulus generalized to both amphetamine and DOM. Taken together with our previous finding that DOM-stimulus generalization occurs to MDA but not to amphetamine, the present study suggests that MDA is capable of producing dual stimulus effects in animals. In addition to these salient features, the results of this study also have an impact on stimulus specificity, and further emphasize the importance of thorough dose-response relationships as related to tests of stimulus generalization.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Further investigation of the discriminative stimulus properties of MDA.
Rats trained to discriminate either (+)-amphetamine or (+/-)-MDA from saline in a two-lever drug discrimination task, were used to study the stimulus effects of MDA and its two optical isomers. Amphetamine-stimulus generalization occurred to S(+)-MDA, but not to its enantiomer R(-)-MDA. This, coupled with our earlier finding of DOM-stimulus generalization to R(-)-MDA but not to S(+)-MDA, suggests that the stimulus effects of S(+)-MDA are predominantly amphetamine-like while those of R(-)-MDA are more DOM-like. Thus, animals trained to discriminate racemic MDA from saline can apparently recognize members of both classes of agents.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Similarity between (+)-amphetamine and amfonelic acid.
Rats, trained to discriminate the CNS stimulant (+)-amphetamine (1.0 mg/kg) from saline in a two-lever drug administration task, were challenged with various doses of the structurally dissimilar CNS stimulant amfonelic acid. Amfonelic acid was found to substitute for the amphetamine stimulus and was found to be 1.5 times more potent than amphetamine.
Animals↗
1-(2,3-Methylenedioxyphenyl)-2-aminopropane (2,3-MDA): a preliminary investigation.
Rats trained to discriminate saline from either (+)-amphetamine, (+/-)-DOM, or (+/-)-3,4-MDA in a two-lever drug discrimination paradigm were administered doses of a novel positional isomer of 3,4-MDA, i.e. 2,3-MDA. The novel isomer produced neither amphetamine-appropriate nor DOM-appropriate responding: the 3,4-MDA stimulus did, however, generalize to 2,3-MDA.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Kinetics of Tn5 transposition.
The kinetics of Tn5 transposition and gene expression were studied. For about 2 h after infection with lambda Tn5, Tn5 transpositions accumulate, reaching a level of about 1.5% of the infected cells. After 2 h transposition is essentially turned off. In cells carrying a resident Tn5, transposition is undetectable after infection. The synthesis of the Tn5-specific proteins p58 and p54 and the kanamycin-resistance protein were studied in pre-irradiated cells infected with lambda Tn5. The synthesis of p58 and p54 peaked early after infection and was significantly reduced, relative to pneo, by 2 h after infection. Moreover, p54 appeared to reach a maximum later than p58. These kinetic data put new constraints on models for the regulation of Tn5 transposition.
Bacterial Proteins↗
A juvenile form of glycerol kinase deficiency with episodic vomiting, acidemia, and stupor.
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Acidosis↗
Structure-activity studies on amphetamine analogs using drug discrimination methodology.
Animals (rats) trained to discriminate 1.0 mg/kg of S(+)-amphetamine sulfate from saline, using a standard operant training procedure, were administered doses of various amphetamine analogs in tests of stimulus generalization in order to study structure-activity relationships (SAR). The types of structural variation of the amphetamine molecule that were investigated included (a) benz-fusion of the aromatic nucleus, (b) alpha-demethylation of the alkyl side chain, (c) conversion of the benzylic methylene to a carbonyl group, and (d) conformational restriction of the side chain. Benz-fusion and alpha-demethylation appear to have a detrimental effect on activity in that none of these analogs produced amphetamine-appropriate responding. However, the carbonylated analog, i.e., cathinone, was found to be equipotent with amphetamine. Furthermore, as with amphetamine, the S-isomer of cathinone was found to be more active than its enantiomer. With respect to the conformationally-restricted analogs, the most potent compound was 2-aminotetralin which was about half as active as racemic amphetamine.
Alkaloids↗
Synthesis and evaluation of a novel series of N,N-dimethylisotryptamines.
A novel series of N,N-dimethylisotryptamine (isoDMT) derivatives, i.e., derivatives of 1-[2-(dimethylamino)ethyl]indole, was prepared and found to be isosteric with their corresponding N,N-dimethyltryptamine (DMT) counterparts with respect to serotonin receptor (rat fundus) affinity. Whereas the isoDMT derivatives possessed a greater affinity than did their corresponding DMT derivatives, they were relatively ineffective in displacing [3H]-5-HT binding from rat brain (cortex) homogenates. In a drug discrimination paradigm, using rats as subjects, 6-OMe-isoDMT produced effects similar to those of 5-OMe-DMT. Attempts to antagonize the discriminative stimulus effects of the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) using two of the isoDMT derivatives proved unsuccessful.
Animals↗
Morphological correlates of transformation in cultured C3H/10T1/2 mouse embryo cells.
In efforts to determine common and consistent morphological parameters of transformation in C3H/10T1/2 cells, 15 cell lines transformed by different carcinogens were examined with the scanning electron microscope (SEM) and compared to non-transformed cells. Cell lines were studied at different passages, at different cell densities, and after growth as anchorage dependent or independent cultures. The transformed cell lines could be distinguished in the SEM from non-transformed cultures by the expression of one or more of the following morphological characteristics: formation of mini- or macro-foci (random piling of cells on top of each other), pleiomorphism in cell size and shape, and cell surface complexity. The extent to which these characteristics were expressed varied widely in the different transformed cell lines. Light microscopic scoring for different types of foci also revealed broad variability among the different transformed lines. At the SEM level, cell lines could not be characterized as transformed on an individual cell basis. However, all transformed cell lines could be definitively characterized as transformed on a population basis due to the presence of mini-foci. The various transformed cell lines were classified semi-quantitatively into categories based on the extent of expression of the different morphological characteristics. There was broad correspondence between the morphological classification and the relative plating efficiencies of the cell lines in soft agarose.
Animals↗
N-Nitroso(2-hydroxyethyl)glycine, a urinary metabolite of N,N-dinitrosopiperazine with potential utility as a monitor for its formation in vivo from piperazine.
Urinary metabolites in the rat of the carcinogen N,N-dinitrosopiperazine were identified as N-nitroso(2-hydroxyethyl)-glycine (22% of the dose), N-nitrosodiethanolamine (3%), 3-hydroxy-N-nitrosopyrrolidine (3%), and unchanged N,N-dinitrosopiperazine (18%). N-Nitroso(2-hydroxyethyl)glycine (1.6 mumol) was detected by gas chromatography-nitrosamine specific detection in the urine of rats treated by gavage with 19 mumol of piperazine and 191 mumol of sodium nitrite. Since sensitive methods are available to quantify N-nitroso(2-hydroxyethyl)glycine in rat urine and human urine, it has potential utility as a monitor for in vivo formation of N,N-dinitrosopiperazine.
Animals↗
Teaching and funding of primary care education in third-year clerkships.
The authors in this article describe a 12-week primary care elective for third-year medical students. The administrative and teaching resources of the Boston University School of Medicine, clinical sites at three Boston community health centers, and federal/state and private foundation funding are coordinated to provide a longitudinal, integrated experience in ambulatory pediatrics and medicine. A literature review revealed no prior medical student programs combining psychiatric, pediatric, and internal medicine teaching in a community setting. Case vignettes and questionnaire results indicate that the program has been a success at introducing students to primary care and the biopsychosocial model. The implications of bridging disciplines as well as academic and community health centers and providing funding resources are discussed. The authors recommend this integrative model for enhancing the development of future primary care physicians.
Boston↗
Formation of cyclic 1,N2-propanodeoxyguanosine adducts in DNA upon reaction with acrolein or crotonaldehyde.
Acrolein reacted with deoxyguanosine at pH 7 and 37 degrees to give three major products, Adducts 1 to 3, which were separated by high-performance liquid chromatography. They were identified by their ultraviolet, mass, and nuclear magnetic resonance spectra, by the spectra of the corresponding guanine derivatives, and by chemical transformations. Adducts 1 and 2 were two rapidly equilibrating diastereomers of 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-6- hydroxypyrimido [1,2-a]purine-10(3H)one, and Adduct 3 was 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8- hydroxypyrimido [1,2-a]purine-10(3H)one. Adducts 1 and 2 were formed by Michael addition of N-1 of deoxyguanosine to C-3 of acrolein, followed by ring closure between N2 of deoxyguanosine and C-1 of acrolein. Adduct 3 was formed by ring closure in the opposite direction. Adduct 3 was analogous to the major crotonaldehyde-deoxyguanosine adducts which were previously characterized. Adduct 3 (0.2 mmol/mol DNA-P) or the corresponding crotonaldehyde adduct (0.03 mmol/mol DNA-P) was formed when either acrolein or crotonaldehyde was allowed to react with DNA at pH 7 and 37 degrees. These results demonstrate that cyclic 1,N2-propanodeoxyguanosine adducts are formed by reaction of acrolein and crotonaldehyde with DNA.
Acrolein↗
Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities.
Sixty-five patients with high-grade soft tissue sarcomas of the extremities were treated in a prospective randomized trial evaluating the efficacy of adjuvant chemotherapy with doxorubicin, cyclophosphamide, and high-dose methotrexate. Local therapy was administered using either amputation or wide local resection plus radiation therapy and the chemotherapy was begun in the immediate postoperative period. Actuarial analysis with median follow-up of 653 days revealed an advantage in continuous disease-free and overall survival in the patient group receiving chemotherapy (P = 0.0008 and P = 0.04, respectively, one-sided Mantel-Haenszel test). The continuous disease-free survival at three years is 92% in the chemotherapy group compared to 60% in the no chemotherapy group. Overall survival is 95% and 74% in these two patient groups. Fifty-eight percent of patients had limb-sparing surgery plus radiation therapy and 42% underwent amputation. In both treatment subgroups analyzed separately, chemotherapy resulted in an improvement in disease-free survival compared to randomized controls not receiving chemotherapy (P = 0.006 and P = 0.04 for groups receiving amputation and limb sparing, respectively). There were no local failures in the patients receiving chemotherapy and two local failures in the no chemotherapy group. The results of this trial confirm the historically controlled pilot trial performed in 26 patients between 1975 and 1977. A current update of the patients in the pilot trial, with a minimum four-year follow-up, reveals an improvement in disease-free and overall survival due to chemotherapy (P less than 0.002). Analysis of the previous pilot trial indicates that only few recurrences are seen beyond three years. Thus, it appears that adjuvant chemotherapy should be a part of the treatment adult patients with soft tissue sarcomas of the extremities.
Adult↗
Antagonism of the effects of the hallucinogen DOM and the purported 5-HT agonist quipazine by 5-HT2 antagonists.
Rats trained to discriminate 1.0 mg/kg of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline in a two-lever operant choice task were administered doses of mescaline, LSD, 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT), quipazine, TFMPP and RU-24969. The DOM-stimulus generalized to the three hallucinogenic agents and to quipazine, but not to the purported serotonin agonists TFMPP or RU-24969. Pretreatment of the animals with the 5-HT2 antagonists ketanserin and pirenperone antagonized the effect produced by DOM. Pirenperone also blocked DOM-stimulus generalization to mescaline, LSD, 5-OMe DMT and quipazine. The results of this study suggest that the discriminative stimulus effects of DOM, the three hallucinogenic agents to which DOM-stimulus generalization occurred, and quipazine, may involve those sub-populations of serotonin receptors that are labeled by tritiated ketanserin (i.e. 5-HT2 sites).
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
Evidence for triiodothyronine receptors in human endometrium and myometrium.
Thyroid gland dysfunction in humans may cause various female reproductive tract disorders. Thyroid hormone action is thought to be mediated by high-affinity low-capacity receptor proteins located in the nucleus. The studies detailed in this report were undertaken to determine if uterine nuclei contain specific high-affinity receptors for thyroid hormone. Nuclei from human endometrium and myometrium were prepared by homogenization and centrifugation following routine surgical procedures. With the use of isolated nuclei, binding experiments with 125I-triiodothyronine (T3) revealed a dissociation constant of approximately 1 X 10(-9) M in both endometrium and myometrium with a maximum number of binding sites equivalent to 0.06 and 0.21 pmol/mg of DNA, respectively. The solubilized binding sites were destroyed largely by trypsin treatment. Competition experiments revealed the following relative binding affinities for these nuclear binding sites: L-T3 greater than D-T3 greater than L-thyronine greater than reverse T3. These results indicate the presence in the human uterus of specific high-affinity binding sites with characteristics expected of a T3 receptor and thus raise the possibility that thyroid hormone may exert effects on the uterus through these receptors.
Binding Sites↗
Indolealkylamine and phenalkylamine hallucinogens. Effect of alpha-methyl and N-methyl substituents on behavioral activity.
Animals (rats), trained to discriminate the hallucinogenic agent 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline in a two-lever operant procedure, were challenged with various doses of several indolealkylamine and phenalkylamine derivatives. In both series, the alpha-methyl analogs were found to be more active than either their N-methyl or alpha-demethyl counterparts. Furthermore, when the activities of the optical isomers of DOM were compared with the activities of S-(+) and R-(-)-alpha-methyltryptamine (alpha-MeT), it was found that the more potent isomer of alpha-MeT (i.e. S) possessed the opposite absolute configuration of the more potent isomer of DOM (i.e. R). With respect to the mechanism of action of these agents, these findings are not inconsistent with a common site hypothesis.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗
DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines.
Stimulus generalization studies were conducted using rats trained to discriminate 1.0 mg/kg of the phenalkylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline in a two-lever operant procedure. The results suggest that certain indolealkylamine hallucinogens, including LSD and several alpha-methyltryptamine, N,N-dialkyltryptamine and beta-carboline derivatives, are capable of producing stimulus effects similar to those produced by DOM. Furthermore, for twelve agents where human data are available, a significant correlation exists between discrimination-derived ED50 values and hallucinogenic potency.
DOM 2,5-Dimethoxy-4-Methylamphetamine↗