Ortho-Methoxyphenylpiperazine

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ortho-Methoxyphenylpiperazine
2-Methoxyphenylpiperazine.svg
Clinical data
Other nameso-Methoxyphenylpiperazine; oMeOPP; 2-Methoxyphenylpiperazine; 2-MeOPP
Drug class Serotonin 5-HT1A receptor agonist; Antipsychotic; Antihypertensive [1] [2]
Identifiers
  • 1-(2-methoxyphenyl)piperazine
CAS Number
PubChem CID
UNII
ChEBI
ChEMBL
Chemical and physical data
Formula C11H16N2O
Molar mass 192.262 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]

Contents

Pharmacology

The drug has been found to have high affinity for the serotonin 5-HT1A receptor, where it acts as a partial agonist (Emax Tooltip 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

Related Research Articles

<span class="mw-page-title-main">Tryptamine</span> Metabolite of the amino acid tryptophan

Tryptamine is an indolamine metabolite of the essential amino acid tryptophan. The chemical structure is defined by an indole—a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon. The structure of tryptamine is a shared feature of certain aminergic neuromodulators including melatonin, serotonin, bufotenin and psychedelic derivatives such as dimethyltryptamine (DMT), psilocybin, psilocin and others.

<span class="mw-page-title-main">Trifluoromethylphenylpiperazine</span> Chemical compound

3-Trifluoromethylphenylpiperazine (TFMPP) is a recreational drug of the phenylpiperazine chemical class and is a substituted piperazine. Usually in combination with benzylpiperazine (BZP) and other analogues, it is sold as an alternative to the illicit drug MDMA ("Ecstasy").

<i>meta</i>-Chlorophenylpiperazine Stimulant

meta-Chlorophenylpiperazine (mCPP) is a psychoactive drug of the phenylpiperazine class. It was initially developed in the late-1970s and used in scientific research before being sold as a designer drug in the mid-2000s. It has been detected in pills touted as legal alternatives to illicit stimulants in New Zealand and pills sold as "ecstasy" in Europe and the United States.

<span class="mw-page-title-main">Naphthylaminopropane</span> Chemical compound

Naphthylaminopropane, also known as naphthylisopropylamine (NIPA), is an experimental drug that was under investigation for the treatment of alcohol and stimulant addiction.

<span class="mw-page-title-main">5-Fluoro-AMT</span> Chemical compound

5-Fluoro-α-methyltryptamine, also known as PAL-212 or PAL-544, is a putative stimulant, entactogen, and psychedelic tryptamine derivative related to α-methyltryptamine (αMT).

α-Methylserotonin Chemical compound

α-Methylserotonin (αMS), also known as α-methyl-5-hydroxytryptamine (α-methyl-5-HT) or 5-hydroxy-α-methyltryptamine (5-HO-αMT), is a tryptamine derivative closely related to the neurotransmitter serotonin (5-HT). It acts as a non-selective serotonin receptor agonist and has been used extensively in scientific research to study the function of the serotonin system.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of one or more monoamine neurotransmitters from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitters and hence enhanced signaling by those neurotransmitters. The monoamine neurotransmitters include serotonin, norepinephrine, and dopamine; monoamine releasing agents can induce the release of one or more of these neurotransmitters.

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons, including dopamine and norepinephrine neurons.

A serotonin–dopamine releasing agent (SDRA) is a type of drug which induces the release of serotonin and dopamine in the body and/or brain.

<span class="mw-page-title-main">Serotonin antagonist and reuptake inhibitor</span> Class of drug

Serotonin antagonist and reuptake inhibitors (SARIs) are a class of drugs used mainly as antidepressants, but also as anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also antagonize α1-adrenergic receptors. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds.

<span class="mw-page-title-main">Phenylpiperazine</span> Chemical compound

1-Phenylpiperazine is a simple chemical compound and drug featuring a phenyl group bound to a piperazine ring. The suffix ‘-piprazole’ is sometimes used in the names of drugs to indicate they belong to this class.

A monoamine reuptake inhibitor (MRI) is a drug that acts as a reuptake inhibitor of one or more of the three major monoamine neurotransmitters serotonin, norepinephrine, and dopamine by blocking the action of one or more of the respective monoamine transporters (MATs), which include the serotonin transporter (SERT), norepinephrine transporter (NET), and dopamine transporter (DAT). This in turn results in an increase in the synaptic concentrations of one or more of these neurotransmitters and therefore an increase in monoaminergic neurotransmission.

<span class="mw-page-title-main">Enciprazine</span> Chemical compound

Enciprazine is an anxiolytic and antipsychotic of the phenylpiperazine class which was never marketed. It shows high affinity for the α1-adrenergic receptor and 5-HT1A receptor, among other sites. The drug was initially anticipated to produce ortho-methoxyphenylpiperazine (oMeOPP), a serotonin receptor agonist with high affinity for the 5-HT1A receptor, as a significant active metabolite, but subsequent research found this not to be the case.

Substituted piperazines are a class of chemical compounds based on a piperazine core. Some are used as recreational drugs and some are used in scientific research.

<i>ortho</i>-Methylphenylpiperazine Chemical compound

ortho-Methylphenylpiperazine (also known as oMPP, oMePP, 1-(2-methylphenyl)piperazine, 2-MPP, and 2-MePP) is a psychoactive designer drug of the phenylpiperazine group. It acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), with EC50 values for induction of monoamine release of 175 nM for serotonin, 39.1 nM for norepinephrine, and 296–542 nM for dopamine. As such, it has about 4.5-fold preference for induction of norepinephrine release over serotonin, and about 7.6- to 13.9-fold preference for induction of norepinephrine release over dopamine.

<span class="mw-page-title-main">5-Fluoro-AET</span> Chemical compound

5-Fluoro-AET, also known as 5-fluoro-α-ethyltryptamine or by the code name PAL-545, is a substituted tryptamine derivative which acts as a serotonin–dopamine releasing agent (SDRA) and as an agonist of the serotonin 5-HT2A receptor.

<span class="mw-page-title-main">Alpertine</span> Abandoned antipsychotic

Alpertine is a drug described as an antipsychotic, neuroleptic, and tranqulizer which was never marketed.

<span class="mw-page-title-main">Milipertine</span> Abandoned antipsychotic

Milipertine is a drug described as an antipsychotic, neuroleptic, and tranquilizer which was under development for the treatment of schizophrenia but was never marketed.

<span class="mw-page-title-main">Solypertine</span> Abandoned sympatholytic drug

Solypertine, also known as solypertine tartrate in the case of the tartrate salt, is a drug described as an antiadrenergic and as also potentially possessing neuroleptic properties which was never marketed.

<span class="mw-page-title-main">BK-NM-AMT</span> Monoamine releaser and entactogen

BK-NM-AMT, or βk-NM-αMT, also known as β-keto-N-methyl-αMT or as α,N-dimethyl-β-ketotryptamine, is a serotonin–dopamine releasing agent (SDRA) and putative entactogen of the tryptamine and α-alkyltryptamine families. Along with certain other tryptamines, such as α-ethyltryptamine (αET), 5-chloro-αMT and 5-fluoro-αET, it is one of the few SDRAs known.

References

  1. 1 2 3 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. 1 2 3 4 5 6 7 8 9 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. 1 2 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.
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