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{{Short description|Opioid analgesic drug}}
{{Distinguish|PPAP (disambiguation){{!}}PPAP}}
{{Drugbox {{Drugbox
| verifiedrevid = 444039722 | verifiedrevid = 447994304
| IUPAC_name = 4-phenyl-1-(2-phenylethyl)piperidin-4-yl acetate | IUPAC_name = 4-Phenyl-1-(2-phenylethyl)piperidin-4-yl acetate
| image = PEPAP.svg | image = PEPAP.svg
| width = 160 | width = 160
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| pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = | pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_AU = S9
| legal_BR = F1
| legal_CA = <!-- Schedule I --> | legal_CA = <!-- Schedule I -->
| legal_UK = Class A | legal_UK = Class A
| legal_US = Schedule I | legal_US = Schedule I
| legal_status = | legal_DE = Anlage I
| routes_of_administration = | routes_of_administration =


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| ATC_suffix = | ATC_suffix =
| PubChem = 60977 | PubChem = 60977
| KEGG = C22763
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01562 | DrugBank = DB01562
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 54939 | ChemSpiderID = 54939
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = T6LN72I828


<!--Chemical data--> <!--Chemical data-->
| C=21 | H=25 | N=1 | O=2 | C=21 | H=25 | N=1 | O=2
| smiles = O=C(C)OC1(CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3
| molecular_weight = 323.43 g/mol
| smiles = O=C(OC3(c1ccccc1)CCN(CCc2ccccc2)CC3)C
| InChI = 1/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
| InChIKey = BVURVTVDNWSNFN-UHFFFAOYAG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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 | StdInChI = 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
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}} }}


'''PEPAP''' is an ] ] that is an ] of ] (meperidine). '''PEPAP''' ('''phenethylphenylacetoxypiperidine''') is an ] ] that is an ] of ].


It is related to the drug ], with an ''N''-phenethyl group in place of the ''N''-] substitution and an ] ester rather than ]. PEPAP is approximately 6-7 times more potent than morphine in laboratory rats.<ref>{{cite journal | pmid = 14406754 | year = 1960 | last1 = Janssen | first1 = PA | last2 = Eddy | first2 = NB | title = Compounds related to pethidine-IV. New general chemical methods of increasing the analgesic activity of pethidine | volume = 2 | pages = 31–45 | journal = Journal of medicinal and pharmaceutical chemistry}}</ref> PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include ], ] and potentially serious ] which can be life-threatening. It is related to the drug ], with an ''N''-phenethyl group in place of the ''N''-] substitution and an ] ester rather than ]. PEPAP is approximately 6–7 times more potent than morphine in laboratory rats.<ref>{{cite journal | vauthors = Janssen PA, Eddy NB | title = Compounds related to pethidine-IV. New general chemical methods of increasing the analgesic activity of pethidine | journal = Journal of Medicinal and Pharmaceutical Chemistry | volume = 2 | pages = 31–45 | date = February 1960 | pmid = 14406754 | doi = 10.1021/jm50008a003 }}</ref> PEPAP presumably has similar effects to other opioids, producing analgesia, sedation and euphoria. Side effects can include ], ] and potentially serious ] which can be life-threatening.


PEPAP has been found to be a potent ] 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.<ref>{{cite journal | pmid = 12006905 | year = 2002 | last1 = Pritzker | first1 = D | last2 = Kanungo | first2 = A | last3 = Kilicarslan | first3 = T | last4 = Tyndale | first4 = RF | last5 = Sellers | first5 = EM | title = Designer drugs that are potent inhibitors of CYP2D6 | volume = 22 | issue = 3 | pages = 330–2 | journal = Journal of clinical psychopharmacology}}</ref> (Both cocaine and methadone are also ] inhibitors and could, in theory, potentiate the effect.) PEPAP has been found to be a potent ] 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.<ref>{{cite journal | vauthors = Pritzker D, Kanungo A, Kilicarslan T, Tyndale RF, Sellers EM | title = Designer drugs that are potent inhibitors of CYP2D6 | journal = Journal of Clinical Psychopharmacology | volume = 22 | issue = 3 | pages = 330–332 | date = June 2002 | pmid = 12006905 | doi = 10.1097/00004714-200206000-00015 | s2cid = 492513 }}</ref> Both cocaine and methadone are also ] 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 ]. 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.<ref>{{cite journal | pmid = 2786564 | year = 1989 | last1 = Youngster | first1 = SK | last2 = Sonsalla | first2 = PK | last3 = Sieber | first3 = BA | last4 = Heikkila | first4 = RE | title = 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 | volume = 249 | issue = 3 | pages = 820–8 | journal = The Journal of pharmacology and experimental therapeutics}}</ref> 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 ]. 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 ].<ref>{{cite journal | vauthors = Youngster SK, Sonsalla PK, Sieber BA, Heikkila RE | title = 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 | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 249 | issue = 3 | pages = 820–828 | date = June 1989 | pmid = 2786564 }}</ref>


There is evidence that the clandestine manufacturers who produced MPPP in the 1970s (included the tainted batch) went on to produce PEPAP<ref>''The Case of the Frozen Addicts'' (ISBN 0-679-42465-2)</ref> in an attempt to avoid using watched precursors or drug intermediates that were illegal. There is evidence that the clandestine manufacturers who produced MPPP in the 1970s, including the tainted batch, went on to produce PEPAP<ref>{{cite book | title = The Case of the Frozen Addicts | isbn = 0-679-42465-2 | url-access = registration | url = https://archive.org/details/caseoffrozenaddi00lang | vauthors = Langston JW, Palfreman J | year = 1995 | publisher = Pantheon Books }}</ref> in an attempt to avoid using watched precursors or drug intermediates that were illegal.


==References== == See also ==
* ]
{{reflist}}
* ]
* ]
* ]
* ]


== References ==
{{Reflist|2}}


{{opioids}} {{Opioidergics}}


] ]
]
] ]
] ]
] ]

Latest revision as of 11:46, 16 January 2024

Opioid analgesic drug Not to be confused with PPAP. Pharmaceutical compound
PEPAP
Clinical data
Other namesPEPAP
Legal status
Legal status
Identifiers
IUPAC name
  • 4-Phenyl-1-(2-phenylethyl)piperidin-4-yl acetate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H25NO2
Molar mass323.436 g·mol
3D model (JSmol)
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 desmethylprodine.

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. 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. 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.

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.

See also

References

  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): 330–332. doi:10.1097/00004714-200206000-00015. PMID 12006905. S2CID 492513.
  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): 820–828. PMID 2786564.
  4. Langston JW, Palfreman J (1995). The Case of the Frozen Addicts. Pantheon Books. ISBN 0-679-42465-2.
Opioid receptor modulators
μ-opioid
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Agonists
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full list)
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  • Others: Kyotorphin (met-enkephalin releaser/degradation stabilizer)
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