Phenothiazine derivative

A number of phenothiazine derivatives have evolved into potent antihistaminie agents a few important ones are described below  

10-[2-(Dimethylamino) propyl] phenothiazine monohydrochloride lOH-Phenothiazine-10-ethanamine, N, N, a-trimethyl-, monohydrochloride BP USP Em. P, Int. P, Ind. P Pheneigan ( eth) Remsed (Endo) Zipan (Savage) Ganphen (Reid-Provident) Fellozine (O Neal, Jones Feldman) Tixylix (May Baker, U.K.) 

Phenothiazine is first prepared by fusing together diphenylamine and sulphur in the presence of iodine or aluminium trichloride. Promethazine base may be prepared by reacting the resulting phenothiazine 

It has a prolonged duration of action. It may be used effectively in perennial and seasonal allergic rhinitis, vasomotor rhinitis, allergic conjunctivitis due to inhalant allergens and foods and certain milder type of skin manifestations of urticaria. It also possesses some anticholinergic, antiserotoninergic, and marked local anaesthetic properties. 

10-(2-Dimethylaminopropyl) phenothiazine compound of 8-chlorotheophylline Promethazine chlorotheophyllinate BP BPC USP  

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MoriciZine. Moricizine, a phenothiazine derivative, was synthesized and developed in Russia, where it has been in general use since 1971. EDA approval of the new dmg application (NDA) for use in the United States was granted in 1991. It is effective against atrial and ventricular arrhythmias (1,2,21). 

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

A more polar phenothiazine derivative in which the side chain consists of an amino amide... 

As the hydrochloric acid salt of the obtained phenothiazine derivative is difficultly soluble In water, the further processing was carried out by way of the acetate. The etheric solution wes extracted several times in e sepereting funnel with dilute ecetic acid. The combined aqueous extracts were basified, extracted with ether, dried with potessium cerbonate end, after removel of the ether, distilled in vecuo. 

Fig 1 Chromatogram of imipramine and phenothiazine derivatives after staining with Forrest reagent [4] 1 = imipramine, 2 = desipramine, 3 = clomipramine, 4 = lofepramine, 5 = trimipramine, 6 = thioridazine, 7 = chlorphenethazine, 8 = periciazine, 9 = promazine, 10 = promethazine. 

Note The colors obtained are characteristic for the various substance classes (Table 1). Thus color tones obtained for phenothiazine derivatives are mainly reddish [1], If the j chromatogram zone contains more than 10 pg substance per spot there is only a colored 1 outer ring surrounding an uncolored center (Fig. 1) [1, 4]. The Forrest reagent does not interfere with subsequent detection with the Dragendorff reagent [1, 4], 1... 

Fig 2 Chromatogram of dibenzoazepine and phenothiazine derivatives after staining with F( REST reagent 1 = fluphenazine, 2 = periciazine, 3 = promethazine, 4 = alimemazine, 5 = mixtur of substances 1 to 4, 6 = mixture of substances 7 to 12, 7 = dibutil, 8 = levomepromaziMi 9 = chlorpromazine, 10 = verophene, 11 - dixjrazine, 12 = perphenazine. 

In 1952 reserpine, an alkaloid extract from the Indian snakewort plant, Rauwolfia serpentina, which had been used in that country to treat madness , was first tried in schizophrenia. The beneficial impact on patients and the hospital wards was dramatic, as was that a year later of chlorpromazine, a phenothiazine derivative and haloperidol, a butyrophenone. These latter two drugs and closely related derivatives remained the mainstay of therapy for almost 40 years. 

Murthy. K. S. Zografi, G., Oil-water partitioning of chlorpromazine and other phenothiazine derivatives using dodecane and n-octanol, J. Pharm. Sci. 59, 1281-1285 (1970). 

Under these conditions, and to test the generalizing capacity of the selected network for the simultaneous determination of phenothiazine derivatives subject... 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

The answer is b. (Hardman, pp 282—283J Central dopamine receptors are divided into Dt and D2 receptors. Antipsychotic activity is better correlated to blockade of D2 receptors. Haloperidol, a potent antipsychotic, selectively antagonizes at Dz receptors. Phenothiazine derivatives, such as chlorpromazine, fluphenazine, and promethazine, are not selective for D2 receptors. Bromocriptine, a selective D2 agonist, is useful in the treatment of parkinsonism and hyperprolactinemia. It produces fewer adverse reactions than do nonselective dopamine receptor agonists... 

ATP inhibits only 6-PGDH and not G-6-PDH (G10). As previously reported for other enzymes, phenothiazine derivatives inhibit both G-6-PDH and 6-PGDH competitive with NADP since NADP protects G-6-PDH depending on its concentration (C4). Neither inhibiting nor activating action has been observed in phenylbutazone treatment (F2). 

Some phenothiazine derivatives (tranquilizers) can be hallucinogenic at high doses (e.g., imipramine (Tofranil) at oral dose of about 1 g and Ethopropazine (Parsidol) at 100 mg). 

Unsymmetrical dimers may also be elec-trochemically produced as illustrated in Schemes 126, 127, and 128 respectively, from phenothiazine derivatives [236], tetra-hydrocarbazole [146] and dihydrobenzaze-pine derivatives [140],... 

Tesafova, E. and Bosikova, Z., Comparison of enantioseparation of selected benzodiazepine and phenothiazine derivatives on chiral stationary phases based on P-cyclodextrin and macrocyclic antibiotics, J. Sep. ScL, 26, 661, 2003. 

Dixon and Mountain reported that exposure of mice to ozone at 1 ppm for 5 h resulted in a depletion of lung histamine content to as low as 75% of the control value 5 days later. They also observed that pretreatment with promethazine, an antihistaminic agent, resulted in a decrease in the amount of pulmonary edema produced by a sublethal dose of ozone. However, promethazine, in addition to being a potent antihistaminic agent, is a phenothiazine derivative and thus might act to trap fiee radicals or stabilize membranes. 

The electron-transfer reactions between the /3-cyclodextrin (/3-CD) N-substituted phenothiazine derivatives and /3-CD.ATPO (4-acetoxy-2,2,6,6-tetramethyl-1-oxopiperidinium hexachloroantimonate) were found to be influenced by the conformations of the phenothiazine derivatives restricted by the /3-CD cavity. N-Phenylphenothiazine (PPT) and A-phenylethylphenothiazine (PEPT), included by /3-CD, can transfer an electron to the /S-CD.ATP complex. No electron transfer was observed between the /3-CD.A-benzylphenothiazine (/3-CD.BPT) complex under the same conditions. The conformation of the /3-CD.BPT complex is such that the oxidation centre was shielded by the /3-CD wall and the substituent. However, electron-transfer reactions between y-CD.BPT and /3-CD.ATP and nitric acid occurred. ... 

Phenothiazine derivatives. Comparison of the structures in Scheme 1.37 can lead to a prediction that hexa(anisyl)-l,3,5-triaminobenzene is more similar to 10,10 -(l,3-phenylene) diphenothiazine than to 10,10 -(l,4-phenylene)diphenothiazine. Nevertheless, on one-electron oxidation, these two isomeric diphenothiazines give dication-diradicals (Okada et al. 1996, Sun et al. 2004). As shown, m-phenylenediphenothaizine has a singlet state, and p-phenylenediphenothiazine has a triplet state. Both diphenothiazine dication-diradicals... 

Q82 Buccastem consists of prochlorperazine, a phenothiazine derivative, v/hich is presented as tablets that are to be placed high betv/een the upper lip and gum and allov/ed to dissolve there. It may be used in the treatment of nausea and vomiting associated v/ith migraine, as absorption from the stomach, v/hich is usually delayed in migraine, is avoided. 

The conventional (or classical) neuroleptics comprise two classes of compounds with distinctive chemical structures 1. the phenothiazines derived from the antihistamine promethazine (prototype chlorpromazine), including Ltillmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and conditions of license. 

Phenothiazine derivatives are nonselective, competitive Dj and D2 antagonists that block dopamine activity on corresponding receptor sites. In addition, their action is... 

Dihydroindolone derivatives do not structurally belong to any of the classes of drugs examined above. Flowever, their mechanism of action, indications of use, and side effects are very similar to phenothiazine derivatives. 

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