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{{Short description|Opioid analgesic drug}} |
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{{Distinguish|PPAP (disambiguation){{!}}PPAP}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 444039722 |
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| verifiedrevid = 447994304 |
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| IUPAC_name = 4-phenyl-1-(2-phenylethyl)piperidin-4-yl acetate |
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| IUPAC_name = 4-Phenyl-1-(2-phenylethyl)piperidin-4-yl acetate |
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| image = PEPAP.svg |
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| image = PEPAP.svg |
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| width = 160 |
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| width = 160 |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_AU = S9 |
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| legal_BR = F1 |
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| legal_CA = <!-- Schedule I --> |
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| legal_CA = <!-- Schedule I --> |
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| legal_UK = Class A |
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| legal_UK = Class A |
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| legal_US = Schedule I |
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| legal_US = Schedule I |
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| legal_status = |
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| legal_DE = Anlage I |
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| routes_of_administration = |
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| routes_of_administration = |
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| ATC_suffix = |
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| ATC_suffix = |
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| PubChem = 60977 |
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| PubChem = 60977 |
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| KEGG = C22763 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB01562 |
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| DrugBank = DB01562 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 54939 |
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| ChemSpiderID = 54939 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = T6LN72I828 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=21 | H=25 | N=1 | O=2 |
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| C=21 | H=25 | N=1 | O=2 |
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| smiles = O=C(C)OC1(CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3 |
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| molecular_weight = 323.43 g/mol |
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| smiles = O=C(OC3(c1ccccc1)CCN(CCc2ccccc2)CC3)C |
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| 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 |
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| InChIKey = BVURVTVDNWSNFN-UHFFFAOYAG |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| 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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| 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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}} |
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}} |
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'''PEPAP''' is an ] ] that is an ] of ] (meperidine). |
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'''PEPAP''' ('''phenethylphenylacetoxypiperidine''') is an ] ] that is an ] of ]. |
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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. |
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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. |
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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.) |
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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. |
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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> |
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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> |
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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. |
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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. |
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==References== |
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== See also == |
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* ] |
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{{reflist}} |
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* ] |
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* ] |
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* ] |
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== References == |
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{{Reflist|2}} |
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{{opioids}} |
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{{Opioidergics}} |
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