Norpethidine (normeperidine, pethidine intermediate B) is a

4-phenylpiperidine 4-Phenylpiperidine is a chemical compound. It features a benzene ring bound to a piperidine ring. 4-Phenylpiperidine is the base structure for a variety of opioids, such as pethidine (meperidine), ketobemidone, alvimopan, loperamide, and dipheno ...

derivative that is both a

precursor Precursor or Precursors may refer to: *Precursor (religion), a forerunner, predecessor ** The Precursor, John the Baptist Science and technology * Precursor (bird), hypothesized genus of fossil birds that was composed of fossilized parts of unre ...

to, and the toxic

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

of,

pethidine Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a fully synthetic opioid pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemist Ot ...

(meperidine). It is scheduled by UN

Single Convention on Narcotic Drugs The Single Convention on Narcotic Drugs, 1961 (Single Convention, 1961 Convention, or C61) is an international treaty that controls activities (cultivation, production, supply, trade, transport) involving specific narcotic drugs and lays down a ...

. It is a Schedule II Narcotic controlled substance in the United States and has an ACSCN of 9233. The 2014 annual manufacturing quota was . Norpethidine is a controlled drug because of its potential uses in manufacturing both pethidine itself and a range of ''N''-substituted derivatives, but it has little

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

activity in its own right. Instead, norpethidine acts as a stimulant and causes

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...

Bioaccumulation Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance faster than it can be lost or eliminated by catabolism and excretion. T ...

of norpethidine is a major complication when pethidine is used in medicine as an

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

, as when pethidine is used in high doses or administered by intravenous infusion, norpethidine can accumulate in the body at a faster rate than it is being excreted, particularly in elderly patients or those with compromised liver or kidney function, resulting in a range of toxic effects, mainly convulsions, but also

myoclonus Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle, a joint, or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus ( myo- "muscle", clonus "spasm") describes a medical sign and, ...

and

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symp ...

. These complications can be serious and have sometimes resulted in death. Metabolism of pethidine to norpethidine is carried out mainly by the CYP enzymes,

CYP2B6 Cytochrome P450 2B6 is an enzyme that in humans is encoded by the ''CYP2B6'' gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances. Func ...

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some ...

and

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

, in the liver, and since the activity of these enzymes can vary between individuals and can be influenced by concurrent use of other drugs, the rate and extent of norpethidine production can be difficult to predict.

Precursor Use

Norpethidine can be used as a precursor in synthesis of other drugs, including

etoxeridine Etoxeridine (Carbetidine, Atenos) is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine). Etoxeridine was developed in the 1950s and investigated for use in surgical anesthesia, how ...

benzethidine Benzethidine is a 4-phenylpiperidine derivative that is related to the clinically used opioid analgesic drug pethidine (''meperidine'', or ''Demerol''). Benzethidine is not currently used in medicine and is a Class A/ Schedule I drug which is ...

furethidine Furethidine is a 4-phenyl piperidine derivative that is related to the clinically used opioid analgesic drug pethidine (meperidine), but with around 25x higher potency. According to another source, Furethidine is 500/30 = 16.7 x the potency of ...

, morpheridine,

anileridine Anileridine (trade name: Leritine) is a synthetic analgesic drug and is a member of the piperidine class of analgesic agents developed by Merck & Co. in the 1950s. It differs from pethidine (meperidine) in that the ''N''-methyl group of meperidin ...

phenoperidine Phenoperidine (Operidine or Lealgin), is an opioid analgesic which is structurally related to pethidine and is used clinically as a general anesthetic. Medical use Phenoperidine is an opioid pain killer—a narcotic analgesic. Pharmacology It i ...

piminodine Piminodine (Alvodine) is an opioid analgesic that is an analogue of pethidine (meperidine). It was used in medicine briefly during the 1960s and 70s, but has largely fallen out of clinical use. It was used particularly for obstetric analgesia an ...

, oxpheneridine,

pheneridine Pheneridine is a 4-phenylpiperidine derivative that is related to the opioid analgesic drug pethidine (meperidine). Pheneridine is not currently used in medicine. Presumably it has similar effects to other opioid derivatives, such as analgesia, ...

carperidine
Legitimate research chemical uses include
R 951R 1187
Janssen, Paul; Jageneau, Anton H. M.; Demoen, Paul J. A.; van De Westeringh, Corn.; De Canniere, Julienne H. M.; Raeymaekers, Alfons H. M.; Wouters, Maria; Sanczuk, Stefan; Hermans, Bert K. F. (1960). "Compounds Related to Pethidine--III. Basic Ketones derived from Norpethidine". Journal of Medicinal and Pharmaceutical Chemistry. 2 (3): 271–280. doi:10.1021/jm50010a003.R 1204
R 1133,R 960
ref name=Janssen1960/> PCP-hybrid
121019-93-0
,Itzhak Y, Kalir A, Weissman BA, Cohen S. New analgesic drugs derived from phencyclidine. J Med Chem. 1981 May;24(5):496-9. doi: 10.1021/jm00137a004. PMID: 7241506.amitriptyline-hybrid

References

{{Serotonergics Convulsants Synthetic opioids Opioid metabolites 4-Phenylpiperidines Carboxylate esters Ethyl esters Human drug metabolites Serotonin–norepinephrine–dopamine reuptake inhibitors

Precursor Use

See also

References