PEPAP

PEPAP
Clinical data
Other names	PEPAP
Legal status
Legal status	AU: S9 (Prohibited substance); DE: Anlage I (Authorized scientific use only); UK: Class A; US: Schedule I;
Identifiers
	IUPAC name 4-Phenyl-1-(2-phenylethyl)piperidin-4-yl acetate;
CAS Number	64-52-8;
PubChem CID	60977;
DrugBank	DB01562 ;
ChemSpider	54939 ;
UNII	T6LN72I828;
CompTox Dashboard (EPA)	DTXSID5048922 ;
Chemical and physical data
Formula	C21H25NO2
Molar mass	323.436 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(C)OC1(CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3;
	InChI InChI=1S/C21H25NO2/c1-18(23)24-21(20-10-6-3-7-11-20)13-16-22(17-14-21)15-12-19-8-4-2-5-9-19/h2-11H,12-17H2,1H3 ; Key:BVURVTVDNWSNFN-UHFFFAOYSA-N ;
	(verify)

PEPAP (phenethylphenylacetoxypiperidine) is an opioid analgesic that is an analog of pethidine (meperidine).

It is related to the drug MPPP, with an N-phenethyl group in place of the N-methyl substitution and an acetate ester rather than propionate. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats.^[1] 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.

PEPAP has been found to be a potent CYP2D6 inhibitor, which makes it likely to cause adverse interactions with some other drugs, although the inhibitory potency of PEPAP is less than that of MPPP.^[2] Both cocaine and methadone are also CYP2D6 inhibitors and could, in theory, potentiate the effect.

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. In animal experiments, only MPTP analogues that preserved the N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine structure were active as dopaminergic neurotoxins. Most structural changes, including replacing the N-methyl group with other substituents, abolished neurotoxicity.^[3]

There is evidence that the clandestine manufacturers who produced MPPP in the 1970s, including the tainted batch, went on to produce PEPAP^[4] in an attempt to avoid using watched precursors or drug intermediates that were illegal.

References

^ Janssen PA, Eddy NB (February 1960). "Compounds related to pethidine-IV. New general chemical methods of increasing the analgesic activity of pethidine". Journal of Medicinal and Pharmaceutical Chemistry. 2: 31–45. doi:10.1021/jm50008a003. PMID 14406754.
^ Pritzker D, Kanungo A, Kilicarslan T, Tyndale RF, Sellers EM (June 2002). "Designer drugs that are potent inhibitors of CYP2D6". Journal of Clinical Psychopharmacology. 22 (3): 330–2. doi:10.1097/00004714-200206000-00015. PMID 12006905.
^ Youngster SK, Sonsalla PK, Sieber BA, Heikkila RE (June 1989). "Structure-activity study of the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. I. Evaluation of the biological activity of MPTP analogs". The Journal of Pharmacology and Experimental Therapeutics. 249 (3): 820–8. PMID 2786564.
^ The Case of the Frozen Addicts. ISBN 0-679-42465-2.

[1] Janssen PA, Eddy NB (February 1960). "Compounds related to pethidine-IV. New general chemical methods of increasing the analgesic activity of pethidine". Journal of Medicinal and Pharmaceutical Chemistry. 2: 31–45. doi:10.1021/jm50008a003. PMID 14406754.

[2] Pritzker D, Kanungo A, Kilicarslan T, Tyndale RF, Sellers EM (June 2002). "Designer drugs that are potent inhibitors of CYP2D6". Journal of Clinical Psychopharmacology. 22 (3): 330–2. doi:10.1097/00004714-200206000-00015. PMID 12006905.

[3] Youngster SK, Sonsalla PK, Sieber BA, Heikkila RE (June 1989). "Structure-activity study of the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. I. Evaluation of the biological activity of MPTP analogs". The Journal of Pharmacology and Experimental Therapeutics. 249 (3): 820–8. PMID 2786564.

[4] The Case of the Frozen Addicts. ISBN 0-679-42465-2.

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