Sedatives and Tranquilizers

Several papers deal with the binary problem of separating sedatives and tranquilizers. While in the first papers a relationship between mass spectrum and biological activity was supposed (Chapter 17.3), the basis in recent papers are structure-activity-relationships. 

Chu C421 used a set of 46 substrueturaI fragments (called augmented atoms ) to describe 30 sedatives and 36 tranquilizers. Classification success rates of various pattern recognition methods were between 85 and 94 %. 

A larger data set (79 sedatives, 140 tranquilizers) was applied by Jurs et. al. C288, 2891 to the calculation of classifiers by a learning machine. A sophisticated preprocessing and feature selection of the raw data improved the predictive ability to 90 %. 

A set of 160 barbiturates was coded using 46 molecular descriptors, including fragments, substructures, environmental descriptors, and a molecular connectivity index C287, 288, 2921. Classifiers were developed with a learning machine that recognizes the duration of the depressant effect- Predictive abilities of 94 % were reported for correct classifications of the duration time less than t minutes . 

Molecular structures have been represented by molecular transforms which are computed from the three-dimensional atomic coordinates of the molecule using X-ray diffraction data C2781. Predictive abilities of 90 X were reported for classifiers developed with the learning machine (data set 72 sedatives, 114 tranquilizers) C276 - 2781. 

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The oxygen atom in these molecules can in many cases be dispensed with as well substitution of sulfur for nitrogen affords a molecule whose salient biologic properties are those of a sedative and tranquilizer. Friedel-Crafts acylation of the n-butyl ether of thiophenol with benzoyl chloride gives the corresponding benzophenone. Reduction of the ketone (15) followed by... 

Cyclization of the side chain onto the nitrogen atom leads to compounds with sedative and tranquilizing activity. The lack of structural specificity, that is, the fact that both positional isomers (41,43) show the same activity, is notable. Thus, condensation of the Grignard reagent from 2-bromopyridine with ben-zophenone affords the tertiary carbinol, 40. Catalytic reduction... 

Furo[3,4-c][l,2,4]triazines 201 were prepared (75USP3962240 77USP-4013767) by condensing furandione 199 with the respective 2-aryl or pyri-dylcarboximidic acid hydrazide 200. Compound 201 (X = N) was oxidized to its N-oxide. Both 200 and 201 have sedative and tranquilizer properties (Scheme 42). 

Parrott AC and Hindmarch I (1975). Arousal and performance - the ubiquitous inverted U relationship. Comparison of changes in response latency and arousal level in normal subjects induced by CNS stimulants, sedatives and tranquillizers. IRCS Medical Science, Clinical Pharmacology and Therapeutics, Psychiatry and Clinical Psychology, 3, 176. 

It exerts sedative and tranquillizing effect and it is postulated that it blocks dopamine receptors within CNS. It is used in acute and chronic psychoses, anxiety disorders, mania and schizophrenia. 

N.A. Alkaloids, tannins, saponins, pectin, oleoresin, aldehydes, dimeric indole alkaloids, vinblastine, sesquiterpenes.100114315 Treat diabetes, leukemia, reduce blood pressure, Hodgkin s disease, hypotensive, sedative and tranquillizing, anticancer. 

In 2000, approximately 14 million Americans— 6.3% of the population—used an illicit drug during the month before the survey. Those surveyed were 12 and older. In the survey, stimulants were included in the category of psychotherapeutic drugs that included pain relievers, sedatives, and tranquilizers. 

Thiatriazole derivatives have been patented for various uses, e.g. as sedatives and tranquilizers (139), as herbicides (142), and as chemosterilants and lubricant additives. 

Lilly employees Stark and Hardison (1985) eventually published Protocol 27 in the Journal of Clinical Psychiatry. They did so without mentioning (a) that four of the five individual centers produced negative results before the data were pruned and pooled, (b) that even the pooled data were negative when Prozac patients taking sedatives and tranquilizers were excluded, (c) that the FDA had many criticisms of the study and its practices, or (d) that even the apparent success of the drug was marginal. The publication by Stark and Hardison claimed that Prozac was comparable to Tofranil in efficacy—a myth that gained considerable currency in the profession—when in fact, the older tricyclic outperformed Prozac most of the time. 

Traditionally sedatives and tranquillizers are classified into groups according to their chemical... 

That approaches be researched to reduce use of hypnotics, sedatives, and tranquilizers. 

Of the other sedatives and tranquillizers, tetrabenazine and related compounds have properties similar to reserpine, including the ability to reduce the monoamine content of brain and phenothiazine derivatives with tranquillizing actions uncouple oxidative phosphorylation and inhibit ATPase activity to an extent roughly corresponding to their tranquillizing... 

Various drugs are invariably used in Parkinsonism for the following effects, first, to lower abnormal reflex rigidity and tremor, and restore normal motor activity e.g., natural atropine group of alkaloids, synthetic atropine substituted, antihistaminics secondly, to minimise mental depression-e.g., analeptics and thirdly, to allay restlessness, tension and anxiety-e.g., sedatives and tranquillizers. 

The wild herb Tanshen Salvia miltiorrhiza Bunge) has been used in traditional Chinese medicine because of its sedative and tranquilizing effects and is also being used to treat coronary heart disease and insomnia. Me range of diterpenoid quinones and quinone precursors have been isolated from Tanshen, including miltirone (56), also known as rosmariquinone, one of the antioxidant components of rosemary (Figure 5.2). °... 

Gupta RC, Kofoed J. Toxicological statistics for barbiturates, otiier sedatives, and tranquillizers in Ontario a 10-year survey. CanMed Assoc J (1966) 863-5. 

Use activity A. is used as an antihypertensive, sedative, and tranquilizer as antihypertensive agent especially in combination with reserpine it exerts a blood pressure lowering effect by widening the blood vessels (vasodilatator), the arterial blood pressure is lowered see also Rauvolfia alkaloids. lit Taylor, in Farnsworth (ed.). The Catharanthus Alkaloids, NewYoric Marcel Dekker 1975. Phytochemistry 18, 965 (1979). 

The structural similarity of azctidinones with barbiturate-type tranquillizers led an Italian team to synthesize and screen 0-lactams of type (264) for possible CNS activity [247-254]. These compounds showed pronounced sedative and tranquillizing activities in rats, mice and dogs, and may be categorized as minor tranquillizers. 

Ting et. al. C299U reported an attempt to correlate the mass spectra of 30 sedatives and 36 tranquilizers with their biological activity. The inass spectral peak intensities at 30 mass numbers were used for the characterization of the compounds. 83 % of the compounds were classified correctly by the nearest neighbour and mapping showed well separated clusters of sedatives and tranquilizers. 

Proelss, H. F., and Lohmann, H. J. Profile of Sedatives and Tranquillizers in Serum as Measured by Gas-Liquid Chromatography... 

Sedatives and tranquilizers— These drugs are sometimes useful in treating people whose bowels are continually agitated as a result of their chronic anxiety and nervous tension. Nevertheless, they are only stopgap measures in critical situations, since they do not remove the underlying cause(s) of the emotional distress. Furthermore, some patients may become so dependent upon the drugs that they cannot function normally without them. 

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