Drugs like MPPP/Ro 2-0718 and PEPAP have been appearing recently on the lists of vendors alongside with U47700 and others. I am not aware if everybody is aware of the dangers associated with these substances.
How many people have encountered these two substance MPPP and PEPAP?
Chemically & structurally similar, they are both derivatives of pethidine/meperidine (Demerol). They are relatively easy to synthesize, and this was one of the principal reasons these particular substances were chosen for synthesis.
MPPP has about 70% of the potency of morphine. The potential for problems is when the reaction temperature raises above 30 °C, in which case an extremely toxic impurity is created called MPTP.
- “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”
- “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 permanent Parkinson symptoms”
“The intermediate tertiary alcohol is liable to dehydration in acidic conditions if the reaction temperature rises above 30 °C. Kidston did not realize this and esterified the intermediate with propionic anhydride at an elevated temperature. Consequently, MPTP was formed as a major impurity”.
“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 permanent Parkinson symptoms.”
In comes PEPAP (phenethylphenylacetoxypiperidine). Due to the bad publicity of MPPP a very similar drug was created, almost a replica of the original chemical structure. PEPAP was reportedly 6-7 times more potent than morphine (in rats).
- “It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the same way as the MPPP byproduct MPTP”
- “It appears that the N-methyl group of MPTP is required for neurotoxic activity.”
- “Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity”
- “There is evidence that the clandestine manufacturers who produced MPPP in the 1970s (included the tainted batch) went on to produce PEPAP in an attempt to avoid using watched precursors or drug intermediates that were illegal.”
How many people have encountered these two substance MPPP and PEPAP?
Chemically & structurally similar, they are both derivatives of pethidine/meperidine (Demerol). They are relatively easy to synthesize, and this was one of the principal reasons these particular substances were chosen for synthesis.
MPPP has about 70% of the potency of morphine. The potential for problems is when the reaction temperature raises above 30 °C, in which case an extremely toxic impurity is created called MPTP.
- “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”
- “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 permanent Parkinson symptoms”
“The intermediate tertiary alcohol is liable to dehydration in acidic conditions if the reaction temperature rises above 30 °C. Kidston did not realize this and esterified the intermediate with propionic anhydride at an elevated temperature. Consequently, MPTP was formed as a major impurity”.
“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 permanent Parkinson symptoms.”
In comes PEPAP (phenethylphenylacetoxypiperidine). Due to the bad publicity of MPPP a very similar drug was created, almost a replica of the original chemical structure. PEPAP was reportedly 6-7 times more potent than morphine (in rats).
- “It is unlikely that the tetrahydropyridine byproducts that may be formed during the synthesis of PEPAP are neurotoxic in the same way as the MPPP byproduct MPTP”
- “It appears that the N-methyl group of MPTP is required for neurotoxic activity.”
- “Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity”
- “There is evidence that the clandestine manufacturers who produced MPPP in the 1970s (included the tainted batch) went on to produce PEPAP in an attempt to avoid using watched precursors or drug intermediates that were illegal.”
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