Diethazine

Of the several syntheses available for the phenothiazine ring system, perhaps the simplest is the sulfuration reaction. This consists of treating the corresponding diphenylamine with a mixture of sulfur and iodine to afford directly the desired heterocycle. Since the proton on the nitrogen of the resultant molecule is but weakly acidic, strong bases are required to form the corresponding anion in order to carry out subsequent alkylation reactions. In practice such diverse bases as ethylmagnesium bromide, sodium amide, and sodium hydride have all been used. Alkylation with (chloroethyl)diethylamine affords diethazine (1), a compound that exhibits both antihista-minic and antiParkinsonian activity. Substitution of w-(2-chloroethyl)pyrrolidine in this sequence leads to pyrathiazine (2), an antihistamine of moderate potency. 

Molnar, Beladii, and Foldes [69] studied antimycobacterial activity of five phenothiazine derivatives including chlorpromazine, levomeprazine, promazine, promethazine, and diethazine. The growth of Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium butyricum was found to be inhibited by chlorpromazine at practically identical concentrations. The minimum inhibitory concentrations for Mycobacterium tuberculosis were chlorpromazine and levomeprazine 10 xg/ml diethazine and promethazine 20 xg/ml whilst chlorpromazine sulphoxide was ineffective even at 100 xg/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on Mycobacterium tuberculosis at 50 xg/ml total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 xg/ml. Preliminary studies in mouse experiments revealed that phenothiazine derivatives were ineffective. 

Molnar et al. [69] studied antibacterial effect and plasmid curing property of several phenothaizines and tried to correlate these functions with respect to their chemical structure. They observed that diethazine, amitriptyline, and impipramine showed bacteriostatic and bactericidal effect on different bacteria. Chlorpromazine sulfoxide and fluorescein were ineffective even at 1000 Ag/ml. The antibacterial compounds deleted at 40-70% frequency the F lac-t- plasmid of Escherichia coli K12 Le-140. Similar plasmid elimination potentiality by phenothiazines was reported by the same group of authors in 1982 [72],... 

Chlorpromazine, diethazine, ethopropa-zine, mequitazine, methdilazine, pera-zine, phenothiazine, prochlorperazine, thiopropazate, trimeprazine... 

Acepromazine, carphenazine, chlorpromazine, diethazine, dimethothiazine, mequitazine, mesoridazine, piperacetazine, prochlorperazine, promethazine, propiomazine, thiazinamium, thiopropazate, thioproperazine... 

Acetophenazine, diethazine, ethopropa-zine (— yellow), fluopromazine, fluphena-zine, metopimazine, pericyazine, phenothiazine, promethazine, thioproperazine, trifluoperazine... 

Acepromazine (- red), adiphenine (-> blue), benorylate, bephenium hydroxynaphthoate, bibenzonium, buclosamide (blue rim), bunamidine, chlorpromazine (-> violet), clefamide (— brown), codeine, colchicine, cyclazocine, cyclomethycaine (— brown), debrisoquine, diaveridine, dibenzepin, diethazine (— violet with excess reagent), diethylthiambutene (-> green-blue), dimethindene, dimethoxanate (— brown), dimoxyline, dipipanone (— blue), dothiepin, doxorubicin, doxycycline (-> yellow), ethopropazine violet), fenpiprane,... 

Clomiphene, diethazine, levomethadyl acetate (— grey-green), methoxamine (- > green)... 

Dose. Diethazine hydrochloride has been given in doses of 0.15 to 1.5 g daily. 

Diethazine hydrochloride, 537 Diethoxyphosphinylthiocholine iodide, 579 Diethoxyphosphinylthioethyltri methylammonium iodide, 579 Diethyl benzenedicarboxylate, 538 Diethyl dimethoxyphosphinothioylthiosuccinate, 717 Diethyl ether, 595... 

Fink, H. Effect of an anticholinergic agent, Diethazine, on BEG and behavior Significance for theory of convulsive therapy. Arch. Neurol. Psychlat. 80 380-387, 1959b. 

The distance between Sites A and C is critical for neuroleptic activity, with a three carbon chain being optimal. Shortening the chain to two carbons has the effect of amplifying the anticholinergic and antihistaminic properties. The amino ethyl derivatives diethazine (2) has proven useful in the treatment of Parkinson s disease, while promethazine (3)is effective as an antihistamine. 

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