MPPP

Desmethylprodine

Legal status
Legal status	DE: Anlage I (Controlled) US: Schedule I
Identifiers
IUPAC name (1-Methyl-4-phenylpiperidin-4-yl) propanoate
Synonyms	4-propionyloxy-4-phenyl-N-methylpiperidine, MPPP, 3-desmethylprodine
CAS Number	13147-09-6
PubChem CID	61583
DrugBank	DB01478 Y
ChemSpider	55493 Y
ChEMBL	CHEMBL279865 Y
Chemical and physical data
Formula	C15H21NO2
Molar mass	247.33 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(CC)OC1(CCN(CC1)C)C2=CC=CC=C2
InChI InChI=1S/C15H21NO2/c1-3-14(17)18-15(9-11-16(2)12-10-15)13-7-5-4-6-8-13/h4-8H,3,9-12H2,1-2H3 Y Key:BCQMRZRAWHNSBF-UHFFFAOYSA-N Y

Desmethylprodine or 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP, Ro 2-0718) is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche. It is an analog of pethidine (meperidine) which the DEA has labeled as a Schedule I drug in the United States. Chemically, it is a reversed ester of pethidine which has about 70% of the potency of morphine. Unlike its derivative prodine, it was not reported to exhibit optical isomerism. It was reported to have 30 times the activity of pethidine and a greater analgesic effect than morphine in rats, and it was demonstrated to cause central nervous system stimulation in mice.

Desmethylprodine was first synthesized in 1947 at Hoffman-LaRoche Laboratories by Albert Ziering and John Lee. They found that it produced effects similar to morphine when administered to rats. Ziering had been searching for synthetic painkillers that were less addictive than morphine. The new drug was a slight variant of pethidine. It was found to be no more effective than pethidine and was never marketed. This research produced the analgesic alphaprodine (Nisentil, Prisilidine), a very closely related compound.

In 1976, a 23-year-old graduate student in chemistry named Barry Kidston was searching for a way to make a legal recreational drug. Having read the paper by Ziering and Lee, he deduced that he could make a drug with pethidine's effects without its legal restrictions, since desmethylprodine is a different molecule and had never been addressed by law. Kidston successfully synthesized and used desmethylprodine for several months, after which he suddenly came down with the symptoms of Parkinson's disease and was hospitalized. Physicians were perplexed, since Parkinson's disease would be a great rarity in someone so young, but L-dopa, the standard drug for Parkinson's, relieved his symptoms. L-dopa is a precursor for dopamine, the neurotransmitter whose lack produces Parkinson's symptoms. It was later found that his development of Parkinson's was due to a common impurity in the synthesis of MPPP called MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin that specifically targets dopamine producing neurons.