MPPP

MPPP (1-methyl-4-phenyl-4-propionoxypiperidine, Desmethylprodine) is an ester of meperidine and is listed as having 70% of the potency of morphine.

The drug was first illicitly synthesised by a graduate student called Barry Kidston. Kidston had apparently studied a 1947 paper by Albert Zeiring. By reversing the ester of the meperidine skeleton, a 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 realise this and esterified the intermediate with propanoic anhydride at room temperature, MPTP was formed as a major impurity.^[1]

1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPP+), a metabolite of MPTP, causes rapid onset of irreversible symptoms similar to Parkinson's Disease.^[2][1] MPTP is metabolized to the neurotoxin MPP+ by the enzyme MAO-B, which is expressed in neurons. This selectively kills brain tissue in the area of the brain called the substantia nigra and causes Parkinsonian symptoms.^[3]

References

1. ^ Johannessen JN, Markey SP. Assessment of the opiate properties of two constituents of a toxic illicit drug mixture. Drug and Alcohol Dependence. 1984 Jul;13(4):367-74.
2. ^ Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ. Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Research. 1979 Dec;1(3):249-54.
3. ^ Schmidt N, Ferger B. Neurochemical findings in the MPTP model of Parkinson's Disease. Journal of Neural Transmission. (2001) 108: 1263–1282.