Ortho-Methoxyphenylpiperazine

Not to be confused with ortho-Methylphenylpiperazine.
ortho-Methoxyphenylpiperazine
Clinical data
Other nameso-Methoxyphenylpiperazine; oMeOPP; 2-Methoxyphenylpiperazine; 2-MeOPP
Drug classSerotonin 5-HT1A receptor agonist; Antipsychotic; Antihypertensive[1][2]
Identifiers
  • 1-(2-methoxyphenyl)piperazine
CAS Number
PubChem CID
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.047.747 Edit this at Wikidata
Chemical and physical data
FormulaC11H16N2O
Molar mass192.262 g·mol−1
3D model (JSmol)
  • COC1=CC=CC=C1N2CCNCC2
  • InChI=1S/C11H16N2O/c1-14-11-5-3-2-4-10(11)13-8-6-12-7-9-13/h2-5,12H,6-9H2,1H3
  • Key:VNZLQLYBRIOLFZ-UHFFFAOYSA-N

ortho-Methoxyphenylpiperazine (oMeOPP), also known as 2-methoxyphenylpiperazine (2-MeOPP), is a phenylpiperazine derivative which is known to act as a serotonergic agent.[1][2] Along with various other phenylpiperazines, like benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP), oMeOPP has been found in illicit drug samples.[3]

Pharmacology

The drug has been found to have high affinity for the serotonin 5-HT1A receptor, where it acts as a partial agonist (EmaxTooltip maximal efficacy ≈ 70%), but shows no affinity for the serotonin 5-HT2 receptor or the dopamine receptors.[1][2][4] This is in contrast to the related drug meta-chlorophenylpiperazine (mCPP), which shows high affinity for both the serotonin 5-HT1A and 5-HT2 receptors.[5][2]

oMeOPP and mCPP have both been found to suppress conditioned avoidance responses (CARs) without markedly affecting escape behavior in animals, indicative that they have antipsychotic-like effects.[2] The serotonin receptor antagonist metergoline reversed the suppression of CARs by mCPP but not by oMeOPP.[2] oMeOPP also reversed amphetamine-induced stereotypy in animals, whereas mCPP did not do so.[2] The suppression of CARs by oMeOPP may be mediated by serotonin 5-HT1A receptor activation.[6][2]

In contrast to other related phenylpiperazines, which are known to act as monoamine releasing agents and/or reuptake inhibitors, the activities of oMeOPP at the monoamine transporters do not appear to have been described.[7][8][9][10][11]

History

oMeOPP was studied in the 1950s as an antihypertensive agent and produced side effects such as drowsiness that could be interpreted as antipsychotic-like.[2][12][13]

Other drugs

oMeOPP has been said to be a metabolite of a variety of drugs including dropropizine, enciprazine, milipertine, MJ-7378, oxypertine, and urapidil.[14][15][16][17] Certain other drugs, such as solypertine, also contain oMeOPP within their chemical structures.[18] However, subsequent research found that oMeOPP is not a metabolite of enciprazine.[16]

See also

References

  1. ^ a b c Glennon RA (1992). "Concepts for the design of 5-HT1A serotonin agonists and antagonists". Drug Development Research. 26 (3). Wiley: 251–274. doi:10.1002/ddr.430260306. ISSN 0272-4391.
  2. ^ a b c d e f g h i Martin GE, Elgin RJ, Kesslick JM, Baldy WJ, Mathiasen JR, Shank RP, et al. (November 1988). "Block of conditioned avoidance responding in the rat by substituted phenylpiperazines". European Journal of Pharmacology. 156 (2): 223–229. doi:10.1016/0014-2999(88)90325-1. PMID 3240768.
  3. ^ White P (2010). Crime Scene to Court: The Essentials of Forensic Science. Royal Society of Chemistry. p. 370. ISBN 978-1-84755-882-4. Retrieved 30 October 2024.
  4. ^ Lyon RA, Titeler M, McKenney JD, Magee PS, Glennon RA (May 1986). "Synthesis and evaluation of phenyl- and benzoylpiperazines as potential serotonergic agents". Journal of Medicinal Chemistry. 29 (5): 630–634. doi:10.1021/jm00155a008. PMID 3701781.
  5. ^ Gatch MB (August 2003). "Discriminative stimulus effects of m-chlorophenylpiperazine as a model of the role of serotonin receptors in anxiety". Life Sciences. 73 (11): 1347–1367. doi:10.1016/s0024-3205(03)00422-3. PMID 12850497.
  6. ^ Evenden JL (1992). "Effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) after repeated administration on a conditioned avoidance response (CAR) in the rat". Psychopharmacology. 109 (1–2): 134–144. doi:10.1007/BF02245491. PMID 1365647. Martin et al. (1988) tested the rather less selective, substituted phenyl piperazine 5-HT agonists, OMPP (ortho-methoxyphenylpiperazine) and MCPP (meta-chlorophenylpiperazine) in a lever-press CAR test, and came to the conclusion that the impairment in CAR induced by OMPP was mediated by the compound's interaction at the 5-HT1A binding site. In passing, it may be noted that the 5-HT1A agonist, buspirone, also impairs CAR, although this effect may be due to the dopamine D2 antagonist effects of this drug (Allen et al. 1974).
  7. ^ Severinsen K, Kraft JF, Koldsø H, Vinberg KA, Rothman RB, Partilla JS, et al. (September 2012). "Binding of the amphetamine-like 1-phenyl-piperazine to monoamine transporters". ACS Chem Neurosci. 3 (9): 693–705. doi:10.1021/cn300040f. PMC 3447394. PMID 23019496.
  8. ^ Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB (October 2004). "Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain". Ann N Y Acad Sci. 1025: 189–197. doi:10.1196/annals.1316.024. PMID 15542717.
  9. ^ Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB (March 2005). "N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy')". Neuropsychopharmacology. 30 (3): 550–560. doi:10.1038/sj.npp.1300585. PMID 15496938.
  10. ^ Baumann MH, Ayestas MA, Dersch CM, Rothman RB (May 2001). "1-(m-chlorophenyl)piperazine (mCPP) dissociates in vivo serotonin release from long-term serotonin depletion in rat brain". Neuropsychopharmacology. 24 (5): 492–501. doi:10.1016/S0893-133X(00)00221-9. PMID 11282249.
  11. ^ Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, et al. (February 2015). "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug Alcohol Depend. 147: 1–19. doi:10.1016/j.drugalcdep.2014.12.005. PMC 4297708. PMID 25548026.
  12. ^ Schlittler E, Druey J, Marxer A (1962). "Antihypertensive Agents". Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques. Vol. 4. Basel: Birkhäuser Basel. pp. 295–351. doi:10.1007/978-3-0348-7044-3_3. ISBN 978-3-0348-7046-7. PMID 13991862. {{cite book}}: |journal= ignored (help)
  13. ^ Page IH, Wolford RW, Corcoran AC (March 1959). "Pharmacological and clinical observations on 1-(2-methoxypheny1 piperazine)". Archives Internationales de Pharmacodynamie et de Therapie. 119 (1–2): 214–224. PMID 13628280.
  14. ^ Elliott S (2011). "Current awareness of piperazines: pharmacology and toxicology". Drug Testing and Analysis. 3 (7–8): 430–438. doi:10.1002/dta.307. PMID 21744514. Furthermore, oMeOPP is a metabolite of some prescribed drugs: enciprazione, milipertine, urapidil, dropropizine and oxypertine.[1,47]
  15. ^ Caccia S, Notarnicola A, Fong MH, Benfenati E (January 1984). "Identification and quantitation of 1-arylpiperazines, metabolites resulting from side-chain cleavage of (4-substituted aryl-1-piperazinyl)alkyl heterocyclic derivatives in rat plasma and brain". Journal of Chromatography. 283: 211–221. doi:10.1016/s0021-9673(00)96256-3. PMID 6707118.
  16. ^ a b Scatina JA, Lockhead SR, Cayen MN, Sisenwine SF (December 1991). "Metabolic disposition of enciprazine, a non-benzodiazepine anxiolytic drug, in rat, dog and man". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 21 (12): 1591–1604. doi:10.3109/00498259109044408. PMID 1686125.
  17. ^ Benfenati E, Caccia S, Della Vedova F (April 1987). "1-(o-Methoxyphenyl)piperazine is a metabolite of drugs bearing a methoxyphenylpiperazine side-chain". The Journal of Pharmacy and Pharmacology. 39 (4): 312–313. doi:10.1111/j.2042-7158.1987.tb06275.x. PMID 2884299.
  18. ^ "Solypertine". PubChem. Retrieved 30 October 2024.