Prediction of the secondary structure of proteins from their amino acid sequence.

Isolation and synthesis of biologically active carbazole alkaloids

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

Publisher Summary This chapter reviews the studies on the mechanism of tumor promotion in mouse skin by croton oil and phorbol diesters and on the effects of these compounds on cell cultures of various types. The chapter discusses the findings in the field of tumor promoters during mid- 1979 and provides sources in the literature that are useful as background. For an historical perspective of the concept of two-stage carcinogenesis and tumor promotion are described. The demonstration of two distinct stages in experimentally induced cancer in animals suggests that there are two stages in environmentally induced cancer in humans. Tumor induction can be divided into two distinct treatment stages, initiation and promotion, and that the promotion stage is reversible. Compounds with tumor-promoting activity are a class of cocarcinogens that are not themselves mutagenic or carcinogenic but that cause the formation of tumors when applied repeatedly after an irreversible event has been "initiated" by a carcinogen. Prevention of human cancer requires the identification and, wherever possible, the elimination of these agents. Because promotion is a reversible process that requires repeated exposure over a period of time, in contrast to the rapid, irreversible process of initiation by carcinogens, manipulation of promotion would seem to be the best method of cancer prevention. The identification of promoters in the environment, and the elucidation of their mechanisms of action, could lead to prophylactic measures such as the development of drugs specifically designed to interfere with the promotion mechanism and prevent tumor formation.

Tumor promoters and the mechanism of tumor promotion.

Studies examining serotonin (5-hydroxytryptamine; 5HT) in schizophrenia show variable and inconsistent findings, which might reflect the heterogeneity of the disease. When these studies are reviewed in the light of Crow's "two-syndrome" paradigm of schizophrenia, a new trend emerges. It appears that 5HT findings may be related to certain features of Type II schizophrenia such as negative symptoms, degenerative brain changes, and chronicity in the following manner: (1) 5HT2 antagonists, which have recently become available, have been shown to have an antipsychotic effect, particularly on the negative symptom cluster. (2) Decreased levels of 5-hydroxyindoleacetic acid in cerebrospinal fluid have been found to be correlated with cortical atrophy or ventricular enlargement in schizophrenic patients. (3) A subgroup of chronic schizophrenic patients has been shown to have elevated levels of platelet or whole blood 5HT. We propose, then, that 5HT dysfunction might be related to Type II, or negative syndrome, schizophrenia, and that the nature of this dysfunction might involve 5HT postsynaptic receptor hypersensitivity. We further suggest that the pharmacotherapy of schizophrenia should include a 5HT-blocking component, as well as a dopamine-blocking component, and we propose that future research should address the role of selective 5HT receptor hypersensitivity in schizophrenia.

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The Role of Serotonin in Schizophrenia

9-Diazomethylanthracene as a new fluorescence and ultraviolet label for the spectrometric detection of picomole quantities of fatty acids by high-pressure liquid chromatography.

Aus den substituierten Benzaldehyden (I) und Nitroathan (II) entstehen die Nitropropene (III), die mit Eisen/HCI zu den Phenylacetonen (IV) reduziert werden.

Asymmetric synthesis of psychotomimetic phenylisopropylamines.

The serotonin (5-HT) receptor affinities and behavioral (discriminative stimulus) properties of a series of 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropanes (2,5-DMA) were investigated. The substituents at the 4-position included H, OMe, OEt, Me, Et, F, Br, I, and NO2. Substituent lipophilicities (pi values) of these functionalities appear to have a minimal effect on either 5-HT receptor affinity or behavioral activity. Those derivatives previously found to be most potent in human studies possess significant affinity for 5-HT receptors. Furthermore, when rats trained to discriminate (+/-)-1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline were used, generalization was found to occur upon administration of the 4-substituted 2,5-DMA derivatives. Because a direct relationship exists between the ED50 values obtained from these discrimination studies and human hallucinogenic potencies, the discriminative stimulus paradigm, with DOM as a training drug, appears to be a useful tool for comparing the quantitative and qualitative (DOM-like) effects produced by certain hallucinogenic agents.

/pdf/behavioral-and-serotonin-receptor-properties-of-4-4py5sk3dqx.pdf

Behavioral and serotonin receptor properties of 4-substituted derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane.

The incidence and quantities of dimethyltryptamine and O-methylbufotenine were studied in the cerebrospinal fluid of patients suffering acute schizophrenic illnesses and in surgical and neurological control groups. Some schizophrenic patients have higher levels of both amines than do controls, though the differences in distribution did not reach statistical significance in the sample studied. The gas-chromatographic technique used is sensitive at the low picogram level.

R. D. Morin

Papers

9-Diazomethylanthracene as a new fluorescence and ultraviolet label for the spectrometric detection of picomole quantities of fatty acids by high-pressure liquid chromatography.

Asymmetric synthesis of psychotomimetic phenylisopropylamines.

Behavioral and serotonin receptor properties of 4-substituted derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane.

Hallucinogenic N-methylated indolealkylamines in the cerebrospinal fluid of psychiatric and control populations.

Behavioral and Neuropharmacological Actions of N-Aralkylhydroxylamines and Their O-Methyl Ethers