Fluphenazine hydrochloride

A mixture of 50 grams of the above prepared piperazine, 30.1 grams of sodium carbonate and 200 ml of benzene is heated to reflux and treated with 39.5 grams of 3-bromopropanol over 1.5 hours. The resulting mixture is refluxed for 2 hours, then filtered, extracted with dilute hydrochloric acid, basified, extracted with benzene, and the extracts are concentrated and distilled to give 1-benzyloxyethyl-4-(3-hydroxypropyl)-piperazine, BP 188° to 190°C (0.15 mm). The free base is converted to the dihydrochloride salt by treatment of an alcoholic solution with ethereal hydrogen chloride to separate the salt. 

Thionyl chloride (67 grams) is added over 15 minutes to a mixture of 39.5 grams of the above prepared dihydrochloride salt and 400 ml of chloroform. Refluxing for 4 hours, cooling and filtering yieids the dihydrochloride salt of 1-benzyloxyethyl-4-(3-chloropropyl)-piperazine, MP 201° to 202°C. The salt in aqueous solution is basified. Extraction with ether and evaporation of the solvent yields the free base. 

Magnesium (1.3 grams) in 8 m of refluxing tetrahydrofuran is treated with 1 ml of ethyl bromide. A solution of 22.7 grams of 1-benzyloxyethyl-4-(3-chloropropyl)-piperazine in 50 ml of tetrahydrofuran Is added slowly and the mixture is refluxed for 1 hour. 

Smith Kline French Laboratories British Patent 925,538 May 8,1963 Craig, P.N. and Zirkle, C.L. U.S. Patent 3,282,930 November 1,1966 assigned to Smith Kline French Laboratories 

Chemical Name 4-[3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl] propyl] -1-piperazine-ethanol dihydrochloride 

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Diphenhydramine hydrochloride, 3,173 Diphenoxylate hydrochloride, 7,149 Disulflram, 4, 168 Dobutamine hydrochloride, 8,139 Droperidol, 7,171 Echothiophate iodide, 3,233 Epinephrine, 7, 193 Ergotamine tartrate, 6,113 Erythromycin, 8,139 Erythromycin estolate, 1, 101 2, 573 Estradiol valerate, 4,192 Ethambutol hydrochloride, 7,231 Ethynodiol diacetate, 3,253 Fenoprofen calcium, 6,161 Flucytosine, 5,115 Fludrocortisone acetate, 3, 281 Fluorouracil, 2,221 Fluoxymesterone, 7,251 Fluphenazine enanthate, 2, 245 4,523 Fluphenazine hydrochloride, 2,263 4,518 Gluthethimide,5,139 Gramicidin, 8,179 Griseofulvin, 8,219 Halcinonide, 8,251 Halothane, 1, 119 2,573 Hexetidine, 7,277 Hydralazine hydrochloride, 8,283 Hydroflumethiazide, 7,297 Hydroxyprogesterone caproate, 4,209 Hydroxyzine dihydrochloride, 7,319 Iodipamide, 3,333 Isocarboxazid, 2, 295... 

FLUPHENAZINE HYDROCHLORIDE Individualize dosage. The oral dose is approximately 2 to 3 times the parenteral dose. Institute treatment with a low initial dosage increase as necessary. Therapeutic effect is often achieved with doses... 

No precise formula can be given to convert to fluphenazine decanoate use. However, in a controlled multicenter study, oral 20 mg/day fluphenazine hydrochloride was equivalent to 25 mg fluphenazine... 

Phenothiazines, piperazine fluphenazine decanoate fluphenazine enanthate fluphenazine hydrochloride perphenazine prochlorperazine thioproperazine mesylate trifuoperazine hydrochloride... 

Rifkin A, Quitkin F, Rabiner CJ, et al. Fluphenazine decanoate, fluphenazine hydrochloride given orally, and placebo in remitted schizophrenics. I. Relapse rates after one year. Arch Gen Psychiatry 1977 34 43-47. 

Hogarty GE, Schooler NR, Ulrich R, et al. Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride. Arch Gen Psychiatry 1979 36 1283-1294. 

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