Fluphenazine (1 mg/kg; IG, administered from days 6 to 15 of gestation) dihydrochloride induces gestational gestation in ovarian cancer [5]. Fluphenazine (0.125-1 mg/kg; IP, single dose) dihydrochloride antimalarial acetaminophen ST significantly inhibits climbing behavior induced by stereotypic biting [6].

Absorption, Distribution and Excretion
Fluphenazine hydrochloride is rapidly absorbed from the GI tract and from parenteral sites. Following oral or im administration of fluphenazine hydrochloride, the onset of action usually occurs within 1 hour; the duration of action is 6-8 hours. Following administration of a single dose of fluphenazine hydrochloride in one limited study, peak serum fluphenazine concentrations were reached within 1.5-2 or 0.5 hours following im or oral administration, respectively.
Esterification of fluphenazine slows the rate of release of the drug from fatty tissues, thus prolonging the drug's duration of action; administration of the esters in a sesame oil vehicle further delays their rate of release. Following im administration of fluphenazine decanoate in sesame oil, the onset of action occurs within 24-72 hours; the duration of action is usually 1-6 weeks, with an average of 2 weeks.
Phenothiazines are highly bound to plasma proteins.
The distribution and metabolic fate of fluphenazine have not been fully elucidated. Fluphenazine reportedly crosses the blood-brain barrier; radioactivity was present in CSF following im administration of radiolabeled fluphenazine decanoate in 2 individuals.
For more Absorption, Distribution and Excretion (Complete) data for Fluphenazine (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
In dogs and rhesus monkeys, the major fecal metabolite, 7-hydroxyfluphenazine, was isolated and identified by mass spectrometric and NMR measurements, involving synthetic 7- and 8-hydroxyfluphenazines. 7-hydroxyfluphenazine is present in bile of treated dogs and rhesus monkeys as glucuronide.
Degradation of piperazine ring in fluphenazine in vivo leads to formation of gamma-(phenothiazinyl-10)-propylamine and of its ring substituted analogs CF3-gamma-(phenothiazinyl-10)-propylamine and C1-gamma-(phenothiazinyl-10)-propylamine.
Fluphenazine and its principal metabolites, fluphenazine sulfoxide, 7-hydroxyfluphenazine and fluphenazine conjugates were identified in human plasma, urine and feces, following im and oral administration of 25 mg of (14)C-fluphenazine dihydrochloride to patients.
Adult and newborn rats were treated with psychotropic drugs; neuroleptics (fluphenazine, benperidol, pimozide, thiotixen), an ataractic (oxazepam) and an anti- depressant (protriptyline) for periods up to one year or longer. The body weight was monitored, and brain weight, total cerebral lipid content, content of individual phospholipids, incorporation of (32)P into individual phospholipids, and the fatty acids composition of phosphatidylethanolamine were measured. The prolonged treatment with neuroleptics and an antidepressant, but not with oxazepam, produced profound, often biphasic or multiphasic changes in the biochemistry of phospholipids. These changes should be taken into account in discussion of the mechanism of action and side-effects of prolonged treatment with antidepressants and neuroleptics.
For more Metabolism/Metabolites (Complete) data for Fluphenazine (6 total), please visit the HSDB record page.
Fluphenazine has known human metabolites that include 10-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl}-2-(trifluoromethyl)-10H-5'-phenothiazin-5-one.

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Biological Half-Life
... The mean terminal half-life of fluphenazine (+ or - SD) was 16.4 + or - 13.3 hr. ...
Plasma half-life of fluphenazine after a single dose was 14.7 hours in 1 patient given hydrochloride by mouth and 14.9 and 15.3 hours in 2 patients given hydrochloride by intramuscular injection. Half-life was 3.6 and 3.7 days in 2 patients given enanthate intramuscularly and 9.6 and 6.8 days in 2 patients given the decanoate intramuscularly.

Toxicity Summary
Fluphenazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

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Interactions
An increase in insulin dosage or decrease in chlorpromazine dosage may be necessary to maintain control of blood glucose levels in patients receiving insulin ... Other phenothiazines that may increase blood glucose levels include fluphenazine ... .
Concurrent use of imipramine and chlorpromazine may result in increased serum levels of either drug. ... Chlorpromazine inhibits the metabolism of imipramine and nortriptyline. Similar precaution should be observed when other ... phenothiazines are used concurrently ... . /Phenothiazines/
A drug interaction involving ascorbic acid and fluphenazine hydrochloride was reported in a 23 yr old male manic depressive patient. During 13 days patient received replacement ascorbic acid steady state fluphenazine hydrochloride plasma levels declined 25% from baseline. This reduction was associated with escalation of manic behavior. Mechanism by which ascorbic acid replacement lowers fluphenazine hydrochloride plasma levels might involve not only liver enzyme induction but also interactions at the absorptive phase. /Fluphenazine hydrochloride/
QT interval-prolonging medications, including cisapride, erythromycin, and quinidine /may produce/ additive QT interval prolongation increasing the risk of developing cardiac arrhythmias when /concurrently administered with phenothiazines/. /Phenothiazines/
For more Interactions (Complete) data for Fluphenazine (31 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat ip 100 mg/kg
LD50 Rat sc 640 mg/kg
LD50 Mouse oral 220 mg/kg
LD50 Mouse ip 89 mg/kg
LD50 Mouse iv 51 mg/kg

[1]. Behavioral effects of withdrawal of fluphenazine after long-term treatment. Arzneimittelforschung. 1976;26(9):1697-700.

[2]. Methods for study of fluphenazine kinetics in man. J Pharm Pharmacol. 1976 Dec;28(12):869-73.

[3]. Fluphenazine determination in human plasma by a sensitive gas chromatographic method using nitrogen detector. J Chromatogr Sci. 1981 Sep;19(9):439-43.

Therapeutic Uses
Antipsychotic Agents, Phenothiazine; Dopamine Antagonists
Fluphenazine hydrochloride is indicated in the management of manifestations of psychotic disorders. /Included in US product label/
Fluphenazine hydrochloride has not been shown effective in the management of behavioral complications in patients with mental retardation. /Included in US product label/
Variability in response to antipsychotic drug treatment may be caused by variable patient compliance, interactions with other drugs, pharmacokinetic variations and variations in concentration-response relationships at the receptor level. Pharmacokinetic variations may in some cases be compensated by individual dosage adjustments based on plasma drug level measurements. The interpatient variability in response to certain time-course of drug concentrations at the receptor site could hitherto only be assessed by clinical judgement. New methods for in vivo assessment of receptor occupancy hold promise for possible measurement of parameters accounting for at least part of the interindividual variation in drug response at the receptor level. Monitoring of fluphenazine, perphenazine, thiothixene and sulpiride plasma levels by specific chemical assay methods seems to offer some guidance to individualization of drug doses. Definite therapeutic plasma level ranges have not been established for chlorpromazine and haloperidol. However, monitoring plasma levels of chlorpromazine or haloperidol might be of value when drug-induced toxicity is suspected, and as a means of controlling patient compliance.
For more Therapeutic Uses (Complete) data for Fluphenazine (6 total), please visit the HSDB record page.

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Drug Warnings
/Fluphenazine/ should never be given intravenously.
... Extrapyramidal reactions ... fairly common, usually 3 types ... Parkinsonian-like syndrome ... dystonia and dyskinesia, including torticollis, tics, and other involuntary muscle movements ... akathisia, shown by restlessness ... hyperreflexia, reported in newborn ... ./Phenothiazines/
12 patients, 24-62 yr old, developed tardive dyskinesia after receiving fluphenazine from 1-2 months to 10 years. First signs of tardive dyskinesia are reversible and length of time symptoms persist prior to discontinuing is more important than age.
Inappropriate antidiuretic hormone secretion most likely related with fluphenazine enanthate therapy in schizophrenic patient 2 days following im dose of 50 mg patient was admitted to hospital. /Fluphenazine Enanthate/
For more Drug Warnings (Complete) data for Fluphenazine (47 total), please visit the HSDB record page.

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Pharmacodynamics
Fluphenazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Fluphenazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.

C22H26F3N3OS

510.440

509.128

C, 51.77; H, 5.53; Cl, 13.89; F, 11.17; N, 8.23; O, 3.13; S, 6.28

146-56-5

Fluphenazine-d8 dihydrochloride; Fluphenazine decanoate; 5002-47-1; Fluphenazine; 69-23-8; Fluphenazine dimaleate; 3093-66-1

3372

White to off-white solid powder

568.3ºC at 760mmHg

200-202ºC

297.5ºC

9.41E-14mmHg at 25°C

5.852

1

8

6

30

544

0

S1C2=C([H])C([H])=C([H])C([H])=C2N(C2C([H])=C(C(F)(F)F)C([H])=C([H])C1=2)C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])O[H])C([H])([H])C1([H])[H]

MBHNWCYEGXQEIT-UHFFFAOYSA-N

InChI=1S/C22H26F3N3OS.2ClH/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29;;/h1-2,4-7,16,29H,3,8-15H2;2*1H

2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;dihydrochloride

Anatensol; Fluphenazine hydrochloride; Mirenil; Lyorodin; Fluphenazine dihydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~195.91 mM)
DMSO : ≥ 38 mg/mL (~74.45 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (195.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)