Desmethylprodine

Desmethylprodine
"MPPP" redirects here. For other uses, see MPPP (disambiguation).
Desmethylprodine
Systematic (IUPAC) name
(1-methyl-4-phenylpiperidin-4-yl) propanoate
Clinical data
Pregnancy cat.  ?
Legal status Schedule I (US)
Identifiers
CAS number 13147-09-6
ATC code  ?
PubChem CID 61583
DrugBank DB01478
ChemSpider 55493 YesY
ChEMBL CHEMBL279865 YesY
Synonyms 4-propionyloxy-4-phenyl-N-methylpiperidine, MPPP, 3-desmethylprodine
Chemical data
Formula C15H21NO2 
Mol. mass 247.33 g/mol
SMILES eMolecules & PubChem
 YesY(what is this?)  (verify)

1-Methyl-4-phenyl-4-propionoxypiperidine (MPPP) or Desmethylprodine is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche[1]. 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.[2] 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.[3] 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.[4]

1-Methyl-4-phenylpyridinium (MPP+), a metabolite of MPTP, causes rapid onset of irreversible symptoms similar to Parkinson's Disease.[5][6] 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.[7]

References

  1. ^ US Patent 2498432 - I. Branched Lower Alkyl-4-Phenyl-4-Aceloxy Piperidines
  2. ^ Ziering, A.; Lee, J. (1947). "Piperidine derivatives; 1,3-dialkyl-4-aryl-4-acyloxypiperidines". The Journal of organic chemistry 12 (6): 911–914. doi:10.1021/jo01170a024. PMID 18919744.  edit
  3. ^ Johannessen, J. N.; Markey, S. P. (1984). "Assessment of the opiate properties of two constituents of a toxic illicit drug mixture". Drug and alcohol dependence 13 (4): 367–374. doi:10.1016/0376-8716(84)90004-8. PMID 6148225.  edit
  4. ^ Gibb, Barry J. (2007). The Rough Guide to the Brain, Rough Guides Ltd., London, pg.166
  5. ^ Davis, G. C.; Williams, A. C.; Markey, S. P.; Ebert, M. H.; Caine, E. D.; Reichert, C. M.; Kopin, I. J. (1979). "Chronic Parkinsonism secondary to intravenous injection of meperidine analogues". Psychiatry research 1 (3): 249–254. doi:10.1016/0165-1781(79)90006-4. PMID 298352.  edit
  6. ^ Wallis, Claudia (2001-06-24). "Surprising Clue to Parkinson's - TIME". Time. http://www.time.com/time/magazine/article/0,9171,1101850408-141542,00.html. Retrieved 2010-05-13. 
  7. ^ Schmidt, N.; Ferger, B. (2001). "Neurochemical findings in the MPTP model of Parkinson's disease". Journal of neural transmission (Vienna, Austria : 1996) 108 (11): 1263–1282. doi:10.1007/s007020100004. PMID 11768626.  edit
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