MPPP
Encyclopedia
1-Methyl-4-phenyl-4-propionoxypiperidine (MPPP) or Desmethylprodine is an opioid
analgesic
drug developed in the 1940s by researchers at Hoffmann-La Roche
. It is not used in clinical practice, but has been illegally manufactured for recreational drug use
. It is an analog
of meperidine (Demerol), but, since it is not used in medicine, the DEA
has labeled it a Schedule I drug in the United States
. In fact, it is the reversed ester
of pethidine
and is listed as having 70% of the potency of morphine
.
The drug was first synthesised in 1977 for recreational purposes by a 23-year old graduate student named Barry Kidston. Kidston had studied a 1947 paper by Albert Ziering. By reversing the ester of the meperidine skeleton, a then-legally uncontrolled drug approaching the potency of morphine was produced.
However, the intermediate tertiary alcohol is liable to dehydration in acidic conditions if the reaction temperature rises above -30°C, and, since Kidston did not realize this and esterified the intermediate with propionic anhydride at room temperature, MPTP
was formed as a major impurity. Several days after trying this new batch of his homemade drug, Kidston developed serious Parkinson's Disease
symptoms, as did several friends he had shared the drug with.
1-Methyl-4-phenylpyridinium (MPP+
), a metabolite of MPTP, causes rapid onset of irreversible symptoms similar to Parkinson's Disease
. MPTP
is metabolized to the neurotoxin MPP+ by the enzyme MAO-B, which is expressed in glial cells. This selectively kills brain tissue in the area of the brain called the substantia nigra
and causes Parkinsonian symptoms.
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
drug developed in the 1940s by researchers at Hoffmann-La Roche
Hoffmann-La Roche
F. Hoffmann-La Roche Ltd. is a Swiss global health-care company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange....
. It is not used in clinical practice, but has been illegally manufactured for recreational drug use
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...
. It is an analog
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of meperidine (Demerol), but, since it is not used in medicine, the DEA
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...
has labeled it a Schedule I drug in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. In fact, it is the reversed ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
of pethidine
Pethidine
Pethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Indonesia); Petidin Dolargan (in Poland);...
and is listed as having 70% of the potency of morphine
Morphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
.
The drug was first synthesised in 1977 for recreational purposes by a 23-year old graduate student named Barry Kidston. Kidston had studied a 1947 paper by Albert Ziering. By reversing the ester of the meperidine skeleton, a then-legally uncontrolled drug approaching the potency of morphine was produced.
However, the intermediate tertiary alcohol is liable to dehydration in acidic conditions if the reaction temperature rises above -30°C, and, since Kidston did not realize this and esterified the intermediate with propionic anhydride at room temperature, MPTP
MPTP
MPTP is a neurotoxin precursor to MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain...
was formed as a major impurity. Several days after trying this new batch of his homemade drug, Kidston developed serious Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
symptoms, as did several friends he had shared the drug with.
1-Methyl-4-phenylpyridinium (MPP+
MPP+
MPP+ is a positively charged molecule with chemical formula C12H12N+. It is toxic and acts by interfering with oxidative phosphorylation in mitochondria, causing depletion of ATP and cell death...
), a metabolite of MPTP, causes rapid onset of irreversible symptoms similar to Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. MPTP
MPTP
MPTP is a neurotoxin precursor to MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain...
is metabolized to the neurotoxin MPP+ by the enzyme MAO-B, which is expressed in glial cells. This selectively kills brain tissue in the area of the brain called the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
and causes Parkinsonian symptoms.