General Description
Odorless white or off-white crystalline powder. Tasteless at first, but slightly bitter aftertaste. pH (aqueous solution) 8.2.
Reactivity Profile
PHENYLBUTAZONE(50-33-9) is incompatible with strong oxidizers, strong acids and strong bases. .
Air & Water Reactions
This compound is relatively stable at ambient temperatures. Aqueous decomposition of this chemical occurs by hydrolysis and oxidation. Insoluble in water.
Fire Hazard
Flash point data for this chemical are not available; however, PHENYLBUTAZONE is probably combustible.
Description
Phenylbutazone, one of the earliest NSAIDs
introduced, is now indicated for the symptomatic
relief of rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, gout, and
acute superficial thrombophlebitis. The gastrointestinal and bone marrow toxicity observed in its early use have been greatly
reduced by lower dosage (300 mg/d). Nevertheless, it is used primarily where other drugs have
failed and then only for short-term therapy. The
drug has a long serum half-life of about 100 h. It
is a moderately active cyclooxygenase inhibitor
and it suppresses both spontaneous and chemotactic motility of neutrophils. In addition to the
serious gastrointestinal and hematological adverse effects, sodium and water retention, rash,
vertigo, and dermatitis are observed.
Chemical Properties
Off-Whtie Solid
Originator
Butazolidin, Geigy ,US,1952
Uses
A non-steroidal anti-inflammatory compound. An inhibitor of cyclooxygenase that is also a substrate for peroxidation by cyclooxygenase
Uses
An inhibitor of Cox.
Uses
For the treatment of backache and ankylosing spondylitis
Uses
Phenylbutazone, a nonsteroidal anti-inflammatory drug, is an efficient reducing cofactor for the peroxidase activity of COX. Phenylbutazone-dependent inactivation of COX and prostacyclin synthase is markedly increased in the presence of 100 μM hydrogen peroxide with half-maximal effects at Phenylbutazone concentrations of 100 and 25 μM for COX and prostacyclin synthase, respectively.
Definition
ChEBI:Phenylbutazone is a member of the class of pyrazolidines that is 1,2-diphenylpyrazolidine-3,5-dione carrying a butyl group at the 4-position. It has a role as a non-narcotic analgesic, a non-steroidal anti-inflammatory drug, an antirheumatic drug, a peripheral nervous system drug, a metabolite and an EC 1.1.1.184 [carbonyl reductase (NADPH)] inhibitor.
Manufacturing Process
7.6 parts of sodium are dissolved in 190 parts by volume of absolute alcohol; 65 parts of diethyl-n-butyl malonate and 65 parts of hydrazobenzene are added. The alcohol is slowly distilled off and the reaction mixture heated for 12 hours at a bath temperature of 150°C and finally in vacuo, until no more alcohol comes off.
The product is dissolved in water, clarified with a little animal charcoal and 15% hydrochloric acid is slowly added until an acid reaction to Congo red paper is produced. 1,2-Diphenyl-3,5-dioxo-4-n-butyl-pyrazolidine separates as an oil, which rapidly become crystalline. It crystallizes from alcohol as colorless needles with a MP of 105°C.
Brand name
Azolid (Sanofi Aventis); Butazolidin (Novartis);Algesin;Algirreudin;Algoverine;Alka butazolidin;Alkabutazone;Alka-phenylbutazone;Alka-sterazolidin;Anarthral;Apophenylbutazone;Apo-phenylbutazone;Arteopan;Arthirikin;Artibrin;Artrisin;Artrodesmol extra;Bizolin 20;Bizolin 700;Butacal;Butacol;Butadilat;Butadin;Butadyne;Butafenil;Butagros;Butakvertin;Butaparin;Butaphen;Buta-phen;Butarex;Butartiril;Butatril;Butazolidin alka;Butazolidina;Butial;Butinol;Butiwas;Buto beta;Butoroid cream;Butrex;Carudol;Celestalgon;Celestazone;Colfezone;Corbuvit;Dartranol;Debutazon;Delta-butazolidin;Delta-demoplas;Delta-myogit;Delta-tomanol;Deltawaukobuzon;Dephimixn;Dexa tomanol;Dexa-attritin;Dexa-escopyrin;Dexamed;Dexatrzona;Dibuzon;Direstop;Ditrone;Doctofril;Dolosin dexa;Dolpirina;Ectobutazone;Ethibute;Exraheudon;Exrheudon;F 650;Fenibutina;Flebosil;Glycyl;Hepabuzon;Inflazone;Intrabuzone;Mammyl;Megazone;Mepha-butazone;Mepropyrin;Mi 540;Naupax;Neuro-demoplas;Neuzoline m;Novobutazone;Oluprin;Oppazoen;Osadrinim;Parazolidin;Parzolidon;Pasirheuman;Penetradol;Phenbuff;Phenbutazone;Phenylarthrite;Phenylbetazone;Phenylon plus;Phlebolan;Pirabutil;Pirarreumol-b;Pirarreumol-p;Prebutex;Precirhemin;Prednirheumin;Proxyfezone;Proydynam;Pyrbutal;Ranocor;Reopin;Reumilene;Rheopyrin;Rheosolon;Rheumanoln;Rheumaphen;Rheumycalm;Salzone;Servizolidin;Sigma-elmedal;Sintobutina;Stabilat;Tevocodyn;Tibutazone;Ticinil calcio;Ticinil calico;Trabit;Zolapelin;Zolidinium.
Therapeutic Function
Antiinflammatory, Antiarthritic
World Health Organization (WHO)
Phenylbutazone, a pyrazolone derivative with anti-inflammatory,
analgesic and antipyretic activity, was introduced in 1949 for the treatment of
rheumatic disorders. Its use was subsequently associated with serious and
sometimes fatal adverse reactions, notably cases of aplastic anaemia and
agranulocytosis. Many national drug regulatory authorities consider that more
recently introduced drugs offer a safer alternative for most, if not all, patients
requiring anti-inflammatory agents. Phenylbutazone has thus been either
withdrawn at the national level or retained with rigorously restricted indications for
patients unresponsive to other therapy. These restrictions also apply, in general, to
combination products containing phenylbutazone.
Biochem/physiol Actions
Phenylbutazone is a hepatotoxin and binds to plasma proteins. It is used to treat inflammation in horse. Phenylbutazone has potential to treat ankylosing spondylitis. It has therapeutic potential to treat myotonic dystrophy type 1 (DM1) by inducing muscle blind-like protein 1 (MBNL1) expression. It also favors the expression of muscle chloride channel in skeletal muscles.
Clinical Use
Phenylbutazone is a
nonsteroidal anti-inflammatory drug used for
the acute treatment of ankylosing spondylitis,
chronic polyarthritis, and gout. Because of
severe side effects including disturbances of
the hematopoietic system like agranulocytosis
and aplastic anemia the use is limited
to conditions in which other nonsteroidal antiinflammatory
drugs do not show sufficient efficacy.
Phenylbutazone is given as oral, rectal,
intramuscular or topical formulation (up to 600
mg/d initial dose, up to 400 mg/d maintenance
dose). The peak plasma concentration is reached
2 h after oral application. Phenylbutazone is
bound to 98% to plasma protein. Oxyphenbutazone
is formed as an active metabolite of phenylbutazone.
Synthesis
Phenylbutazone, 4-butyl-1,2-diphenyl-3,5-pyrazolidinedione (3.2.6),
is synthesized in a single stage by reacting hydrazobenzol with butylmalonic ester
[68,69].
Veterinary Drugs and Treatments
One manufacturer lists the following as the indications for phenylbutazone:
“For the relief of inflammatory conditions associated
with the musculoskeletal system in dogs and horses.” (Package
Insert; Butazolidin?—Coopers). It has been used primarily for the
treatment of lameness in horses and, occasionally, as an analgesic/
antiinflammatory, antipyretic in dogs, cattle, and swine.
Purification Methods
Crystallise the dione from EtOH. Its pK2 3 is 4.52 (in H2O), 4.89 (in 50% aqueous EtOH) and 5.25 (80% 2-methoxyethanol). It complexes with Hg2+, Cd2+ and Zn2+. It has UV with max at 239.5nm in MeOH+50% aqueous HClO4 and 264nm in aqueous 0.1N NaOH. [Beilstein 24 III/IV 1123.]
