Thiazines pheno

Tetran itro ph en oth iazine (Pheno thiazine Tetranitrosulfoxide). Yel solid, mp 368°. Can NO, H N02 be prepd in 70% yield by the nitration of phenols thiazine with a mixt of 298% nitric acid and an- hydr sulfuric acid at 60°. 

Amantadine is used cautiously in patients with seizure disorders, hepatic disease, psychosis, cardiac disease, and renal disease The antihistamines, pheno-thiazines, disopyramide, and alcohol increase the risk of adverse reactions when administered with amantadine... 

The antiemetics and antivertigo drug may have additive effects when used with alcohol and other CNS depressants such as sedatives, hypnotics, antianxiety drugp, opiates, and antidepressants. There may be additive anticholinergic effects (see Chap. 25) when administered with drag s that have anticholinergic activity such as the antihistamines, antidepressants, pheno-thiazines, and disopyramide The antacids decrease absorption of the antiemetics. 

Synthetic Method 5 2-benzenesulfonyl-3-(p-carbethoxyanilino)pheno-thiazine (13o) (procedure from U.S. Patent 4,710,570).Sb To a warm, stirred solution of 1.8 g of dye 3-(4-carbethoxyphenylimino)-3//-pheno-thiazine in 50 ml of tetrahydrofuran was added 0.8 g of benzenesulfinic acid (obtained by adding dilute hydrochloric acid to an aqueous solution of benzenesulfinic acid sodium salt to cause precipitation of the free acid). After stirring 1 h at 40°C the solvent was evaporated off under reduced pressure. The yellowish solution was poured into water. The precipitate was filtered, washed repeatedly with distilled water and methanol. Recrystallization from methanol gave 1.9 g (76%) of the leuco dye 2-benzenesulfonyl-3-(4-car-bethoxyanilino)phenothiazine (13o) as a yellowish powder. 

Anticholinergic agents antihistamines, antiparkinsonian agents, tricyclic antidepressants, pheno-thiazines... 

R. R. Gupta and M. Kumar, in Bioactive Molecules. Vol. 4. Pheno-thiazines and 1,4-Benzothiazines Chemical and Biomedical Aspects (R. R. Gupta, ed.) p. 1. Elsevier, Amsterdam, 1988. 

As mentioned in CHEC(1984), phenothiazine derivatives are best known as pharmaceuticals for the central nervous system, and are used not only for treatment of various mental illnesses <1986AXC1083> but also as neuroleptics, sedatives, analgesics, anti-emetics, and antihistamines <1987AXC1737>. A review has appeared on use of pheno-thiazines in the treatment of Creutzfeldt-Jacob disease <2001JAA411>. 

Scokel, P.W. and Jones, W.D. (1962) Infant jaundice after pheno-thiazine drugs for labor an enigma. Obstet Gynecol 20 124— 127. 

An attempt to alkylate phenothiazine with propargyl bromide using sodium hydride in dimethylformamide afforded a 70% yield of N-( 1 -propynyl)pheno-thiazine instead of the expected JV-(2-propynyl)phenothiazine [7], This reaction (Eq. 33) constituted the first synthesis of an ynamine [7]. Other diaryl-... 

In California, mixer-loaders and spray applicators who work with toxicity category I and II organophosphates or N-methyl carbamates more than 30 hours per 30-day period are required to have medical supervision. Supervision consists of an interview and a medical examination to determine if a medical condition exists which would make the worker unusually susceptible to poisoning due to cholinesterase inhibition, and to caution the individual about the use of certain drugs such as the pheno-thiazine tranquilizers vdtich potentiate the effects of cholinesterase (ChE) inhibition. Two blood samples, taken several days apart, are analyzed to determine the individual s preexposure plasma and red blood cell (RBC) ChE activity (baseline value). The physician arranges a routine ChE testing program and provides for extra ChE tests should the worker be accidently exposed to OP s. If ChE activity is depressed to 50 percent of the baseline value, the physician may ask the employer to place the worker on... 

The coronary vasodilating effect of various substances was compared (142, 147-149). Persch and Nitz (149) studied the therapeutic application of parakhelline for angina pectoris in dogs and cats. Papaverine brought about a maximum blood flow in the coronary arteries much more rapidly than that of khelline which was, however, of longer duration. Fekete and Borsy (150) studied the effect of pheno-thiazine derivatives and of papaverine on the dilation of coronary arteries. 

Gorton and coworkers have been particularly active in this field and produced an excellent review of the methods and approaches used for the successful chemical modification of electrodes for NADH oxidation [33]. They concentrated mainly on the adsorption onto electrode surfaces of mediators which are known to oxidise NADH in solution. The resulting systems were based on phenazines [34], phenoxazines [35, 36] and pheno-thiazines [32]. To date, this approach has produced some of the most successful electrodes for NADH oxidation. However, attempts to use similar mediators attached to poly(siloxane) films at electrode surfaces have proved less successful. Kinetic analysis of the results indicates that this is because of the slow charge transfer between the redox centres within the film so that the catalytic oxidation of NADH is restricted to a thin layer nearest the electrode surface [37, 38]. This illustrates the importance of a charge transfer between mediator groups in polymer modified electrodes. 

Adverse effects Its adverse effects include severe nausea and vomiting (centrally mediated). [Note These effects can be diminished by pretreatment with cannabinoids (see p. 243) or pheno-thiazine (see p. 242).] Severe bone marrow depression limits extensive use. Latent viral infections (for example, Herpes zoster] may appear because of immunosuppression. Extravasation is a serious problem. If it occurs, the area should be infiltrated with isotonic sodium thiosulfite to inactivate the drug. 

Most of the older antidepressants are called tricyclic because their chemical nucleus has the basic tricyclic structure of the original pheno-thiazine neuroleptic, chlorpromazine, or Thorazine (Bassuk et ah, 1977 Pauker, 1981). Of extreme importance, the antidepressant amoxapine (Asendin) is turned into a neuroleptic in the body, producing the same problems as any other neuroleptic, including tardive dyskinesia (chapters 3 and 4). 

The last chapter, Theoretical Studies on Phenothiazines, Benzo[a]pheno-thiazines and Benz[c] acridines by Teruo Kurihara, Kazumi Shinohara, Hidet-sugu Wakabayashi, Noboru Motohashi, Hiroshi Sakagami, and Joseph Mol-nar, presents their quantitative structure-activity relationship (QSAR) analysis for minimum inhibitory concentration (MIC) of phenothiazines and benzo[a]phenothiazines. The MIC values of phenothiazines were well correlated to AAHf, HOMO energy, and /xG. QSAR may be applicable to predict the MIC of phenothiazines. This review could contribute to prediction of the relationship of structure to biological activity. 

FIGURE 10.4 Experimental versus theoretical hyperfine couphngs in phenoxazine, pheno-thiazine, and phenoselenazine. The three points deviating significantly from the bisector line belong to the nuclei. This deviation is likely caused by the lack of vibrational averaging in the calculation. 

NITRATES 1. ANALGESICS-nefopam 2. ANTIARRHYTHMICS -disopyramide, propafenone 3. ANTIDEPRESSANTS-TCAs 4. ANTI EMETICS-cydizine 5. ANTIHISTAMINES -chlorphenamine, cyproheptadine, hydroxyzine 6. ANTIMUSCARINICS -atropine, benzatropine, cydopentolate, dicydover-ine, flavoxate, homat-ropine, hyoscine, orphenadrine, oxybutynin, procyclidine, propantheline, tolterodine, trihexyphenidyl, tropicamide. 7. ANTI-PARKINSON S DRUGS-dopaminergics 8. ANTI-PSYCHOTICS - pheno-thiazines, clozapine, pimozide 9. MUSCLE RELAXANTS-baclofen 1. t risk of antimuscarinic side-effects when isosorbide dinitrate is co-administered with these drugs 2. 1 efficacy of sublingual nitrate tablets... 

PHENOTHIAZINES ADRENERGIC NEURONE BLOCKERS Variable effect some cases of t hypotensive effect other cases where hypotensive effects 1 by higher doses (>100 mg) of chlorpromazine Additive hypotensive effect. Pheno-thiazines cause vasodilatation however, chlorpromazine blocks the uptake of guanethidine into adrenergic neurones Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

ARTEMETHER WITH LUMEFANTRINE 1. ANTIARRHYTHMICS - amiodarone, disopyramide, procainamide, propafenone 2. ANTIBIOTICS -macrolides (especially azithromycin, clarithromycin, parenteral erythromycin, telithromycin), quinolones (especially moxifloxacin), quinupristin/dalfbpristin 3. ANTICANCER AND IMMUNOMODU-LATING DRUGS - arsenic trioxide 4. ANTIDEPRESSANTS - TCAs, venlafax-ine 5. ANTIEMETICS-dolasetron 6. ANTIFUNGALS - fluconazole, posaconazole, voriconazole 7. ANTIHISTAMINES - terfenadine, hydroxyzine, mizolastine 8. ANTIMALARIALS -chloroquine, hydroxychloroquine, mefloquine, quinine 9. ANTIPROTOZOALS -pentamidine isetionate 10. ANTI-PSYCHOTICS - alypicals, pheno-thiazines, pimozide 11. BETA-BLOCKERS - sotalol 12. BRONCHODILATORS-parenteral bronchodilators 13. CNS STIMULANTS - atomoxetine Risk of ventricular arrhythmias, particularly torsades de pointes Additive effect these drugs cause prolongation of the Q-T interval Avoid co-administration... 

Drugs and poisons can be classified alphabetically, pharmacologically (antidiabetic, anticonvulsant, etc.), or by chemical structure (barbiturates, pheno-thiazines, etc.). However, for analytical purposes it is more useful to classify poisons according to the method used for extraction. Five major groups are usually considered ... 

Marquis Test (p. 139). Many basic drugs produce colours with diis reagent. It is a good test for opiates, stimulants, antihistamines, and pheno-thiazines. 

The absolute solubilities and the partition coefficients of pheno-thiazine and of some of its derivatives in the systems heptane-water and cyclohexane-water have been determined. ... 

Another type of analytical application of sulfuric acid oxidation has been developed recently, based on the intense fluorescence which appears when the sulfuric solutions containing oxidized pheno-thiazine derivatives are diluted with dimethyl sulfoxide. It has been shown that concentrations as low as 0.01 /xg/ml may be detected this way and that substituents in position 2 decrease the intensity of the fluorescence to a greater extent than side chains at position 10.1 1... 

The formation of colored products by the action of a variety of oxidating agents has been used for the detection and assay of pheno-thiazine derivatives. The use of chlorpromazine as an indicator... 

Heinecken et found that a series of quinoneiminoid pheno-thiazine dyes, like methylene blue and its analogs, give ESR signals in sulfuric acid, the four lines of which have relative intensities 1 2 2 1. In alkaline solutions the spectrum consists of a 1 1 1 triplet. In both cases high resolutions were achieved with solutions in... 

Dimerization of the Phenothiazinyl Free Radicals It was pointed out in Section IV, B, 3 that the greatest spin density in the molecule of the phenothiazinyl free radicals is located on the nitrogen, sulfur, C-3 and C-7 atoms. Since the sulfur atom of pheno-thiazines is involved in a sulfide bridge, and has, consequently, no tendency to form a third covalence, there are only three kinds of... 

It has long been known that oxidation of phenothiazine and its C-substituted derivatives in aqueous acid yields the red 3H-pheno-thiazin-3-ones (phenothiazones). This reaction proceeds by a nucleophilic attack of water on the intermediate phenazathionium cations. The pathway of Scheme 5, after Shine and Mach, describes the route in detail. 

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