Flupentixol

Flupentixol (INN), also known as

flupenthixol (former BAN), marketed
under brand names such as Depixol
and Fluanxol is a typical antipsychotic
drug of the thioxanthene class. It was
introduced in 1965 by Lundbeck. In
addition to single drug preparations, it
is also available as
flupentixol/melitracen—a combination
product containing both melitracen (a
tricyclic antidepressant) and
flupentixol. Flupentixol is not
approved for use in the United States.
It is, however, approved for use in the
UK,[4] Australia,[5] Canada, Russian
Federation,[6] South Africa, New
Zealand, Philippines and various other
countries.

Flupentixol

Clinical data
Trade names Depixol, Fluanxol
AHFS/Drugs.com Micromedex
Detailed Consumer
Information
Pregnancy AU: C
category
Routes of Oral, IM (including a
administration
depot)
ATC code N05AF01 (WHO )

Legal status
Legal status AU: S4 (Prescription
only)
CA: ℞-only
UK: POM
(Prescription only)
In general:
℞ (Prescription only)
 ℞ (Prescription only)

Pharmacokinetic data
Bioavailability 40–55% (oral)[2]
Metabolism Gut wall, hepatic[1]
Elimination half-life 35 hours[2]

Excretion Renal (negligible)[3]

Identifiers

IUPAC name
(EZ)-2-[4-[3-[2-(trifluoromethyl)thioxanthen-9-ylidene]propyl]piperazin-1-yl]ethanol

CAS Number 2709-56-0  

PubChem CID 5281881

IUPHAR/BPS 968
DrugBank DB00875  

ChemSpider 4445173  

UNII 21HMQ851IS
 21HMQ851IS
KEGG D01044  

ChEMBL ChEMBL42055  

CompTox DTXSID3058749
Dashboard (EPA)
ECHA InfoCard 100.018.459

Chemical and physical data

Formula C23H25F3N2OS
Molar mass 434.52 g·mol−1
3D model (JSmol) Interactive image

SMILES
FC(F)(F)c2cc1C(\c3c(Sc1cc2)cccc3)=C/CCN4CCN(CCO)CC4

InChI
InChI=1S/C23H25F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-
27)14-15-29/h1-2,4-8,16,29H,3,9-15H2/b18-5- 
Key:NJMYODHXAKYRHW-DVZOWYKESA-N 

   (what is this?)  (verify)
Medical uses
Flupentixol's main use is as a long-
acting injection given once in every
two or three weeks to individuals with
schizophrenia who have poor
compliance with medication and
suffer frequent relapses of illness,
though it is also commonly given as a
tablet. There however is little evidence
to support its use for this
indication.[4][7]

Flupentixol is also used in low doses

as an antidepressant.[4][8][9][10][11][12][13]
There is tentative evidence that it
reduces the rate of deliberate self-
harm, among those who self-harm
repeatedly.[14]

Adverse effects
Adverse effect incidence[2][4][5][15][16]

Common (>1% incidence) adverse

effects include
Extrapyramidal side effects such
as: (which usually become apparent
soon after therapy is begun or soon
after an increase in dose is made)
- Muscle rigidity
- Hypokinesia
- Hyperkinesia
- Parkinsonism
- Tremor
- Akathisia
- Dystonia
Dry mouth
Constipation
Hypersalivation — excessive
salivation
Blurred vision
Diaphoresis — excessive sweating
Nausea
Dizziness
Somnolence
Restlessness
Insomnia
Overactivity
Headache
Nervousness
Fatigue
Myalgia
Hyperprolactinemia and its
complications such as: (acutely)
- Sexual dysfunction
- Amenorrhea — cessation of
menstrual cycles
- Gynecomastia — enlargement of
breast tissue in males
- Galactorrhea — the expulsion of
breast milk that's not related to
breastfeeding or pregnancy
and if the hyperprolactinemia
persists chronically, the following
adverse effects may be seen:
- Reduced bone mineral density
leading to osteoporosis (brittle
bones)
- Infertility
Dyspepsia — indigestion
Abdominal pain
Flatulence
Nasal congestion
Polyuria — passing more urine than
usual
Uncommon (0.1–1% incidence)
adverse effects include
Fainting
Palpitations
Rare (<0.1% incidence) adverse
effects include
Blood dyscrasias (abnormalities in
the cell composition of blood), such
as:
- Agranulocytosis — a drop in white
blood cell counts that leaves one
open to potentially life-threatening
infections
- Neutropenia — a drop in the
number of neutrophils (white blood
cells that specifically fight bacteria)
in one's blood
- Leucopenia — a less severe drop
in white blood cell counts than
agranulocytosis
- Thrombocytopenia — a drop in the
number of platelets in the blood.
Platelets are responsible for blood
clotting and hence this leads to an
increased risk of bruising and other
bleeds
Neuroleptic malignant syndrome —
a potentially fatal condition that
appear to result from central D2
receptor blockade. The symptoms
include:
- Hyperthermia
- Muscle rigidity
- Rhabdomyolysis
- Autonomic instability (e.g.
tachycardia, diarrhea, diaphoresis,
etc.)
- Mental status changes (e.g. coma,
agitation, anxiety, confusion, etc.)
Unknown incidence adverse
effects include
Jaundice
Abnormal liver function test results
Tardive dyskinesia — an often
incurable movement disorder that
usually results from years of
continuous treatment with
antipsychotic drugs, especially
typical antipsychotics like
flupenthixol. It presents with
repetitive, involuntary, purposeless
and slow movements; TD can be
triggered by a fast dose reduction in
any antipsychotic.
Hypotension
Confusional state
Seizures
Mania
Hypomania
Depression
Hot flush
Anergia
Appetite changes
Weight changes
Hyperglycemia — high blood
glucose (sugar) levels
Abnormal glucose tolerance
Pruritus — itchiness
Rash
Dermatitis
Photosensitivity — sensitivity to
light
Oculogyric crisis
Accommodation disorder
Sleep disorder
Impaired concentration
Tachycardia
QTc interval prolongation — an
abnormality in the electrical activity
of the heart that can lead to
potentially fatal changes in heart
rhythm
Torsades de pointes
Miosis — constriction of the pupil of
the eye
Paralytic ileus — paralysis of the
bowel muscles leading to severe
constipation, inability to pass wind,
etc.
Mydriasis
Glaucoma
Interactions …

It should not be used concomitantly

with medications known to prolong
the QTc interval (e.g. 5-HT3
antagonists, tricyclic antidepressants,
citalopram, etc.) as this may lead to
an increased risk of QTc interval
prolongation.[16][2] Neither should it be
given concurrently with lithium
(medication) as it may increase the
risk of lithium toxicity and neuroleptic
malignant syndrome.[4][5][16] It should
not be given concurrently with other
antipsychotics due to the potential for
this to increase the risk of side
effects, especially neurological side
effects such as neuroleptic malignant
syndrome.[4][5][16] It should be avoided
in patients on CNS depressants such
as opioids, alcohol and
barbiturates.[16]

Contraindications …

It should not be given in the following

disease states:[2][4][5][16]

Pheochromocytoma
Prolactin-dependent tumors such
as pituitary prolactinomas and
breast cancer
 Long QT syndrome
Coma
Circulatory collapse
Subcortical brain damage
Blood dyscrasia
Parkinson's disease
Dementia with Lewy bodies

Pharmacology
Binding profile[17]
 Protein cis-flupentixol trans-flupentixol

5-HT1A 8028 —

5-HT2A 87.5 (HFC) —

5-HT2C 102.2 (RC) —

mAChRs[18] Neg. Neg.

D1 3.5 474 (MB)

D2 0.35 120

D3 1.75 162.5

D4 66.3 >1000

H1 0.86 5.73

Acronyms used:
HFC — Human frontal cortex receptor
MB — Mouse brain receptor
RC — Cloned rat receptor

Its antipsychotic effects are likely

caused by D2 and/or 5-HT2A
antagonism, whereas its
antidepressant effects at lower doses
may be mediated by preferential
D2/D3 autoreceptor blockade,
resulting in increased postsynaptic
activation.

References
1. Jann, MW; Ereshefsky, L; Saklad,
SR (July–August 1985). "Clinical
pharmacokinetics of the depot
antipsychotics". Clinical
Pharmacokinetics. 10 (4): 315–
333. doi:10.2165/00003088-
198510040-00003 .
PMID 2864156 .
2. "Depixol Tablets 3mg - Summary
of Product Characteristics
(SPC)" . electronic Medicines
 (SPC)" . electronic Medicines
Compendium. Lundbeck Ltd. 27
December 2012. Retrieved
20 October 2013.
3. Balant-Gorgia, A. E.; Balant, L.
(Aug 1987). "Antipsychotic drugs:
clinical pharmacokinetics of
potential candidates for plasma
concentration monitoring".
Clinical Pharmacokinetics. 13 (2):
65–90. doi:10.2165/00003088-
198713020-00001 .
PMID 2887326 .
4. Joint Formulary Committee
(2013). British National Formulary
(BNF) (65 ed.). London, UK:
Pharmaceutical Press. ISBN 978-
 Pharmaceutical Press. ISBN 978-
0-85711-084-8.
5. Rossi, S, ed. (2013). Australian
Medicines Handbook (2013 ed.).
Adelaide: The Australian
Medicines Handbook Unit Trust.
ISBN 978-0-9805790-9-3.
6. "Fluanxol® (flupentixol) Tablets
Registration Certificate" . Russian
State Register of Medicinal
Products. Retrieved 29 July 2014.
7. Shen, X; Xia, J; Adams, CE (Nov
14, 2012). Shen, Xiaohong (ed.).
"Flupenthixol versus placebo for
schizophrenia". Cochrane
Database of Systematic Reviews.
11: CD009777.
 11: CD009777.
doi:10.1002/14651858.CD00977
7.pub2 . PMID 23152280 .
8. Robertson MM, Trimble MR (May
1981). "The antidepressant action
of flupenthixol". The Practitioner.
225 (1355): 761–3.
PMID 7291129 .
9. Pöldinger W, Sieberns S (1983).
"Depression-inducing and
antidepressive effects of
neuroleptics. Experiences with
flupenthixol and flupenthixol
decanoate". Neuropsychobiology.
10 (2–3): 131–6.
doi:10.1159/000117999 .
 PMID 6674820 .
10. Johnson DA (January 1979). "A
double-blind comparison of
flupenthixol, nortriptyline and
diazepam in neurotic
depression". Acta Psychiatrica
Scandinavica. 59 (1): 1–8.
doi:10.1111/j.1600-
0447.1979.tb06940.x .
PMID 369298 .
11. Young JP, Hughes WC, Lader MH
(May 1976). "A controlled
comparison of flupenthixol and
amitriptyline in depressed
outpatients" . British Medical
Journal. 1 (6018): 1116–8.
 doi:10.1136/bmj.1.6018.1116 .
PMC 1639983 . PMID 773506 .
12. Fujiwara J, Ishino H, Baba O,
Hanaoka M, Sasaki K (August
1976). "Effect of flupenthixol on
depression with special reference
to combination use with tricyclic
antidepressants. An uncontrolled
pilot study with 45 patients". Acta
Psychiatrica Scandinavica. 54
(2): 99–105. doi:10.1111/j.1600-
0447.1976.tb00101.x .
PMID 961463 .
13. Tam W, Young JP, John G, Lader
MH (March 1982). "A controlled
comparison of flupenthixol
 comparison of flupenthixol
decanoate injections and oral
amitriptyline in depressed out-
patients". The British Journal of
Psychiatry. 140 (3): 287–91.
doi:10.1192/bjp.140.3.287 .
PMID 7093597 .
14. Hawton, K; Witt, KG; Taylor
Salisbury, TL; Arensman, E;
Gunnell, D; Hazell, P; Townsend,
E; van Heeringen, K (6 July 2015).
"Pharmacological interventions
for self-harm in adults" (PDF).
The Cochrane Database of
Systematic Reviews. 7 (7):
CD011777.
doi:10.1002/14651858.CD01177
 7.
hdl:10536/DRO/DU:30080508 .
PMID 26147958 .
15. Bostwick, JR; Guthrie, SK;
Ellingrod, VL (January 2009).
"ntipsychotic-induced
hyperprolactinemia" (PDF).
Pharmacotherapy. 29 (1): 64–73.
doi:10.1592/phco.29.1.64 .
hdl:2027.42/90238 .
PMID 19113797 .
16. "FLUANXOL® DEPOT
FLUANXOL® CONCENTRATED
DEPOT" . TGA eBusiness
Services. Lundbeck Australia Pty
Ltd. 28 June 2013. Retrieved
 Ltd. 28 June 2013. Retrieved
20 October 2013.
17. Roth, BL; Driscol, J (12 January
2011). "PDSP Ki Database" .
Psychoactive Drug Screening
Program (PDSP). University of
North Carolina at Chapel Hill and
the United States National
Institute of Mental Health.
Archived from the original on 8
November 2013. Retrieved
20 October 2013.
18. Golds PR, Przyslo FR, Strange PG
(March 1980). "The binding of
some antidepressant drugs to
brain muscarinic acetylcholine
receptors" . British Journal of
 receptors" . British Journal of
Pharmacology. 68 (3): 541–9.
doi:10.1111/j.1476-
5381.1980.tb14570.x .
PMC 2044199 . PMID 7052344 .

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