1988 Article:
PEPAP, a synthetic heroin substitute that is 36 times more powerful than pure heroin. PEPAP was developed illegally four years ago as a substitute for another synthetic heroin substitute, MPPP, which was causing neuro-degenerative diseases with symptoms similar to Parkinson's disease. Drugs like PEPAP and MPPP are known as designer drugs because of the way they are made: taking the formula of a controlled narcotic and changing it slightly. Because authorities have been required to specify the makeup of drugs they want declared illegal, these designer drugs - in effect, the chemical cousins of illegal drugs - fell out of reach of the law until 1986, when Congress banned them.

Immediate Effect:
Lochridge said PEPAP causes an immediate effect that includes a heroin-like euphoria "but with a more dreamlike or spacey sensation typical of PCP. There's a disorientation, visual illusion, auditory hallucinations and the blurring of vision." Although it was developed as an alternative to MPPP, the drug appears to produce similar undesireable side effects by selectively killing brain cells, Lochridge said.

Because such drugs are made in extremely concentrated forms, and because quality control is not the hallmark of designer-drug manufacturers, users are exposed to unusually high risks.

"This stuff is super-deadly," Lochridge said. "It is so potent in its pure form that even fumes can kill. . . . It is hard to dilute down to useable strength."

1985 Article:
The Reagan Administration will propose legislation to combat the production of synthetic copies of illegal narcotics and hallucinogens, Attorney General Edwin Meese announced today. He said the Government decided this week to temporarily ban two of the drugs, M.P.P.P. and P.E.P.A.P., which have been linked to the development of Parkinson's Disease and are now legally obtainable. The substances have a similar effect to illegal drugs but are chemically distinct. They represent a dangerous phenomenon in the illicit drug market, Mr. Meese said at a news conference. Many of these designer drugs have a high potential for abuse and their abuse may lead to severe psychological and physical dependence.

A Synthetic Analogue of Meperidine:
Some abused drugs are substrates of CYP2D6 (e.g., paramethoxyamphetamine, methylenedioxy-methamphetamine). CYP2D6 inhibition by concurrently used drugs of abuse could potentiate such drugs and increase acute toxicity. Ten designer drugs were tested as inhibitors of CYP2D6. Only 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) and 1-[2-phenylethyl]-4-phenyl-4-acetoxypiperidine (PEPAP) interacted significantly. Both are synthetic analogues of meperidine sold as "synthetic heroin." No CYP2D6-mediated metabolites were detected for either compound. Concurrent oral use of CYP2D6 substrates with MPPP and PEPAP may represent a kinetic drug interaction risk, but this risk must be confirmed clinically.

An opioid analgesic that is an analog of pethidine (meperidine). It is related to the drug MPPP. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats. PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include itching, nausea and potentially serious respiratory depression which can be life-threatening.

There is evidence that the clandestine manufacturers who produced MPPP in the 1970s, including the tainted batch, went on to produce PEPAP in an attempt to avoid using watched precursors or drug intermediates that were illegal.