Piritramide(R-3365, trade names Dipidolor, Piridolan, Pirium and others) is a synthetic
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
(narcotic painkiller) that is marketed in certain
Europe
Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...
an countries including:
Austria
Austria, , bar, Östareich officially the Republic of Austria, is a country in the southern part of Central Europe, lying in the Eastern Alps. It is a federation of nine states, one of which is the capital, Vienna, the most populous ...
,
Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
,
Czech Republic
The Czech Republic, or simply Czechia, is a landlocked country in Central Europe. Historically known as Bohemia, it is bordered by Austria to the south, Germany to the west, Poland to the northeast, and Slovakia to the southeast. The ...
,
Slovenia
Slovenia ( ; sl, Slovenija ), officially the Republic of Slovenia (Slovene: , abbr.: ''RS''), is a country in Central Europe. It is bordered by Italy to the west, Austria to the north, Hungary to the northeast, Croatia to the southeast, an ...
,
Germany
Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
and the
Netherlands
)
, anthem = ( en, "William of Nassau")
, image_map =
, map_caption =
, subdivision_type = Sovereign state
, subdivision_name = Kingdom of the Netherlands
, established_title = Before independence
, established_date = Spanish Netherl ...
.
It comes in free form, is about 0.75x times as potent as
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
and is given
parenterally
A route of administration in pharmacology and toxicology is the way by which a drug, fluid, poison, or other substance is taken into the body.
Routes of administration are generally classified by the location at which the substance is applied. ...
(by injection) for the treatment of severe pain.
[ Nausea, vomiting, respiratory depression and constipation are believed to be less frequent with piritramide than with ]morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
(the gold standard opioid against which other opioids are compared and contrasted), and it produces more rapid-onset analgesia (pain relief) when compared to morphine and pethidine
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...
. After intravenous administration the onset of analgesia is as little as 1–2 minutes, which may be related to its great lipophilicity
Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
. The analgesic and sedative effects of piritramide are believed to be potentiated with phenothiazines and its emetic (nausea/vomiting-inducing) effects are suppressed.[ The ]volume of distribution
In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...
is 0.7-1 L/kg after a single dose, 4.7-6 L/kg after steady-state concentrations are achieved and up to 11.1 L/kg after prolonged dosing.[
Piritramide was developed and patented in Belgium, at Janssen, in 1960. It is part of an eponymous two-member class of opioids in clinical use with the other being ]bezitramide
Bezitramide is an opioid analgesic. Bezitramide itself is a prodrug which is readily hydrolyzed in the gastrointestinal tract to its active metabolite, despropionyl-bezitramide. Bezitramide was discovered at Janssen Pharmaceutica in 1961. It is m ...
(Burgodin). The closest chemical and structural relatives of piritramide in clinical use include the diphenoxylate
Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine i ...
family, fentanyl
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocaine ...
(both Janssen discoveries) and somewhat more distantly alphaprodine
Prodine (trade names Prisilidine and Nisentil) is an opioid analgesic that is an analog of pethidine (meperidine). It was developed in Germany in the late 1940s.
There are two isomers of the trans form of prodine, alphaprodine and betaprodine. ...
.
Not being in clinical use in the United States, it is a Schedule I Narcotic controlled substance with a DEA ACSCN of 9642 and manufacturing quota of zero.
Synthesis
*This same sidechain is also used in the synthesis of: Bezitramide
Bezitramide is an opioid analgesic. Bezitramide itself is a prodrug which is readily hydrolyzed in the gastrointestinal tract to its active metabolite, despropionyl-bezitramide. Bezitramide was discovered at Janssen Pharmaceutica in 1961. It is m ...
, Diphenoxylate
Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine i ...
, Imidafenacin & others.
*This same piperidine is also used in the synthesis of: Carpipramine
Carpipramine (Prazinil, Defekton) is an atypical antipsychotic used for the treatment of schizophrenia and anxiety in France and Japan. In addition to its neuroleptic and anxiolytic effects, carpipramine also has hypnotic properties. It is stru ...
, Clocapramine
Clocapramine (Clofekton, Padrasen), also known as 3-chlorocarpipramine, is an atypical antipsychotic of the iminodibenzyl class which was introduced in Japan in 1974 by Yoshitomi for the treatment of schizophrenia. In addition to psychosis, cl ...
, Mosapramine
Mosapramine (Cremin) is an atypical antipsychotic used in Japan for the treatment of schizophrenia. It is a potent dopamine antagonist with high affinity to the D2, D3, and D4 receptors, and with moderate affinity for the 5-HT2 receptors.
S ...
& Pipamperone
Pipamperone ( INN, USAN, BAN), also known as carpiperone and floropipamide or fluoropipamide, and as floropipamide hydrochloride ( JAN), is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia and as a slee ...
.
The last step in the synthesis consists of attachment of the sidechain by an Sn2 alkylation between 4-bromo-2,2-diphenylbutanenitrile 9186-58-8(1) and 1,4'-bipiperidine-4'-carboxamide 9633-82-4(2) catalyzed by KI (Finkelstein reaction
The Finkelstein reaction named after the German chemist Hans Finkelstein, is an SN2 reaction (Substitution Nucleophilic Bimolecular reaction) that involves the exchange of one halogen atom for another. It is an equilibrium reaction, but the reac ...
) in the presence of sodium carbonate
Sodium carbonate, , (also known as washing soda, soda ash and soda crystals) is the inorganic compound with the formula Na2CO3 and its various hydrates. All forms are white, odourless, water-soluble salts that yield moderately alkaline solutions ...
base and in anhydrous toluene solvent yielding ' (3)..
References
{{Opioidergics
Opioids
Piperidines
Carboxamides
Nitriles
Mu-opioid receptor agonists
Janssen Pharmaceutica
Belgian inventions