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Analgesic Effects of β-Phenylethylamine and Various Methylated Derivatives in Mice

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Abstract

Administration of β-phenylethylamine (PEA), the simplest endogenous neuroamine, and various methylated PEA derivatives including α-methyl PEA (amphetamine, AMP) elicits analgesia in mice. Five or 20 min after intraperitoneal PEA injection of as little as 6 mg/kg resulted in an increased latency response time (from 2.4 ± 0.4 to 8.5 ± 2.3 or 7.0 ± 3.0 s, respectively) to the thermal stimulus (hot-plate test), which reached statistical significance at the 15 mg/kg (20 min; 13.1 ± 0.4 s) or 25 mg/kg dose (5 min; 15.3 ± 4.1 s). This PEA effect, was dose-dependent (albeit non-linear: 6, 12, 15, 25, 50 and 100 mg/kg), reached the cut-off time of 45 s at the upper PEA dose (5 min), and it was consistently enhanced by pretreatment with the monoamine oxidase inhibitor pargyline (P). Methylated PEA derivatives (15 and 100 mg/kg dose) produced various degrees of analgesia (in decreasing order p-Me PEA > PEA > N,N-diMe PEA > N-Me PEA) which, likewise to PEA itself, were consistently increased by P and declined over time (mice tested 5, 20 and 60 min after amine injection); small but statistically significant o- and β-Me PEA antinociceptive effects (5 min) were observed only at the higher dose (in the presence of P for β-Me PEA). A small analgesic effect was observed after the administration of AMP (5 or 10 mg/kg) which failed, even after P, to reach statistically significance. Independent of the amine and concentration tested, individual compound’s antinociceptive properties were reliably increased by P (exception of AMP), decreased by reserpine (R) or haloperidol (H), and remained essentially unchanged after naloxone (N) administration suggesting the involvement of catecholamines, but not opioid peptides, in their observed analgesic effects. Injection of P + N produced results similar to those seen after P alone. Under the experimental conditions described neither P, R, H or N had any effects by themselves. These findings suggest additional understanding of the mechanism of action responsible for the analgesic effects of these amines would be of interest, leading further to controlled studies on their alleged usefulness as weight reducing agents and sport performance enhancers.

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Abbreviations

PEA:

β-Phenylethylamine

p-Me PEA:

para-Methylphenylethylamine

α-Me PEA:

α-Methylphenylethylamine, AMP

AMP:

Amphetamine

N-Me PEA:

N-methylphenylethylamine

o-Me PEA:

o-methylphenylethylamine

β-MeP EA:

β-methylphenylethylamine

N,N-diMe PEA:

N,N-dimethylphenylethylamine

References

  1. Westfall TC, Westfall DP (2011) Adrenergic agonists and antagonists. In: Brunton LL, Chabner BA, Krollmann BC (eds) Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 12th edn. McGraw Hill, New York, pp 277–333

    Google Scholar 

  2. Shulgin A, Shulgin A (1991) Phenethylamines I have known and loved: a chemical love story. Transform Press, Berkeley

    Google Scholar 

  3. Berry MD (2004) Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem 90:257–271

    Article  CAS  PubMed  Google Scholar 

  4. Mosnaim AD, Wolf ME (eds) (1978) Non-catecholic phenylethylamines. Part 1: phenylethylamine: biological mechanisms and clinical aspects. Marcel Dekker, USA

    Google Scholar 

  5. Mosnaim AD, Wolf ME (eds) (1978) Non-catecholic phenylethylamines. Part 2: phenylethanolamine, tyramines and octopamine. Marcel Dekker, USA

    Google Scholar 

  6. www.healthremedies.com (Accessed 2014, Copyrights 2008-2014)

  7. Fischer EE, Heller BB, Miro AH (1968) Beta-phenylethylamine in human urine. Arzneimittelforschung 18(11):1486

    CAS  PubMed  Google Scholar 

  8. Sabelli HC, Mosnaim AD (1974) Phenylethylamine hypothesis of affective behavior. Amer J Psychiatry 131:695–699

    CAS  Google Scholar 

  9. Wolf ME, Mosnaim AD (1983) Phenylethylamine in neuropsychiatric disorders. Gen Pharmacol 14(4):385–390

    Article  CAS  PubMed  Google Scholar 

  10. Pawar RS, Grundel E, Fardin-Kia AR, Rader JI (2014) Determination of selected biogenic amines in Acacia rigidula plant materials and dietary supplements using LC–MS/MS methods. J Pharmaceutical Biomed Analysis 88:457–466

    Article  CAS  Google Scholar 

  11. Inwang EE, Mosnaim AD, Sabelli HC (1973) Isolation and characterization of phenylethylamine and phenylethanolamine from human brain. J Neurochem 20:1469–1473

    Article  CAS  PubMed  Google Scholar 

  12. Saavedra JM (1974) Enzymatic isotopic assay for and presence of β-phenylethylamine in brain. J Neurochem 22:211–216

    Article  CAS  PubMed  Google Scholar 

  13. Karoum F, Nasrallah H, Potkin S, Chuang L, Moyer-Schwing J, Phillips I, Wyatt RJ (1979) Mass fragmentography of phenylethylamine, m- and p-tyramine and related amines in plasma, cerebrospinal fluid, urine, and brain. J Neurochem 33(1):201–212

    Article  CAS  PubMed  Google Scholar 

  14. Hansen TR, Greenberg J, Mosnaim AD (1980) Direct effect of phenylethylamine upon isolated vascular smooth muscle of the rat. Europ J Pharmacol 63:95–101

    Article  CAS  Google Scholar 

  15. Hauger R, Skolnick P, Martin L (1982) Specific 3Hbeta-phenylethylamine binding sites in rat brain. Eur J Pharmacol 83:147–148

    Article  CAS  PubMed  Google Scholar 

  16. Fehler M, Broadley KJ, Ford WR (2010) Kidd EJ (2010) Identification of trace-amine-associated receptors (TAAR) in the rat aorta and their role in vasoconstriction by β-phenylethylamine. Naunyn Schmiedebergs Arch Pharmacol 82(4):385–398

    Article  Google Scholar 

  17. Boulton AA (1980) Trace amines and mental disorders. Can J Neurol Sci 7:261–263

    CAS  PubMed  Google Scholar 

  18. Mosnaim AD, Callaghan OH, Wolf ME (1981) Determination of non-catecholic phenylethylamines and monomethylated derivatives of phenylethylamines. J Chromatogr Biomed Appl 224:481–487

    Article  CAS  Google Scholar 

  19. Yang HYT, Neff NH (1973) B-Phenylethylamine: a specific substrate for type B monoamineoxidase in brain. J Pharm Exp Therap 187:365–371

    CAS  Google Scholar 

  20. Durden DA, Davis BA (1993) Determination of regional distribution of phenylethylamine and meta- and para-tyramine in rat brain regions and presence in human and dog plasma by an ultra-sensitive negative chemical ion gas chromatography-mass spectrometric (NCI-GC-MS) method. Neurochem Res 18:995–1002

    Article  CAS  PubMed  Google Scholar 

  21. Mosnaim AD, Wolf ME, Zeller EA (1984) Degradation kinetics by MAO of PEA derivatives: a model for the molecular basis of their analgesic and behavioral effects? In: Boulton A, Baker G, Dewhurst W, Sandler M (eds) Neurobiology of trace amines. Humana Press, New Jersey, pp 299–306

    Chapter  Google Scholar 

  22. Chevesich JA, Callaghan OH, Wolf ME, Mosnaim AD (1983) Behavioral effects in mice produced by monosubstituted phenylethylamines. Fed. Proc. Chicago

  23. Mosnaim AD, Callaghan OH, Hudzik T, Wolf ME (2013) Rat brain-uptake index for phenylethylamine and various monomethylated derivatives. Neurochem Res 38(4):842–846

    Article  CAS  PubMed  Google Scholar 

  24. Matsuoka Y, Masafumi S, Toshihiko S, Yasufumi T, Tsutomu U, Kazuhiko K (1988) Characteristics of antinociception induced by noncatecholic phenylethylamine derivatives: the relation of endogenous norepinephrine to phenylethylamine analog-induced antinociception. Japan J Pharmacol 48:263–272

    Article  CAS  Google Scholar 

  25. Lindemann L, Hoener MC (2005) A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol Sci 26(5):274-81. http://www.ncbi.nlm.nih.gov/pubmed/15860375

  26. Berry MD (2007) The potential of trace amines and their receptors for treating neurological and psychiatric diseases. Reviews on Recent Clinical Trials. 2:3–19

    Article  CAS  PubMed  Google Scholar 

  27. Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK (2001) Amphetamine, 3,4methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol 60:1181–1188

    CAS  PubMed  Google Scholar 

  28. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (2001) Trace amines; identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA 98(16):8966–8971

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Maguire JJ, Barriocanal FP, Davenport AP (2002) Are vasoconstrictor responses to tyramine in human blood vessels, in vitro, mediated by the orphan trace amine receptor, TA1. Br J Pharmacol 131:71P

    Google Scholar 

  30. Lewin AH (2006) Receptors of mammalian trace amines. AAPS J 8(1), Article 16:E138–E145, 2006

  31. www.idmu.co.uk/amphetpain.htm Independent Drug Monitoring Unit, UK (Accessed 2014)

  32. www.wada-ama.org World Anti-Doping Agency (Accessed 2014)

  33. Drago F, Caccamo G, Continella G, Scapagnini U (1984) Amphetamine-induced analgesia does not involve brain opioids. Eur J Pharmacol 101(3–4):267–269

    Article  CAS  PubMed  Google Scholar 

  34. Dalal S, Melzack RJ (1988) Potentiation of opioid analgesia by psychostimulant drugs: a review. Pain Symptom Manag 6(4):245–253

    Google Scholar 

  35. Sabelli HC, Vazquez AJ, Mosnaim AD, Madrid-Pedemonte L (1974) 2-Phenylethylamine as a possible mediator for 9-tetrahydrocannabinol-induced stimulation. Nature 248:144–145

    Article  CAS  PubMed  Google Scholar 

  36. Yaksh TL, Wallace MS (2011) Opioids, analgesics and pain management. In: Brunton LL, Chabner BA, Krollmann BC (eds) Goodman and Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw Hill, New York, pp 480–525

    Google Scholar 

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Acknowledgments

This research was supported by The National Migraine Foundation (AM), The State of Illinois Department of Mental Health and Development Disabilities (MW), and Shriners Hospital for Crippled Children Chicago, IL (EAZ). We thank the late Professor E. Albert Zeller for his invaluable input to this work. We greatly appreciate the skilful technical assistance of Dr. K. Arora and Mr. S. Myles. Ref. 21 contains some preliminary work included in this manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Neuroimmunopharmacology Laboratory, Department of Cellular and Molecular Pharmacology, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, N. Chicago, IL, 60064, USA

    Aron D. Mosnaim

  2. Abbvie, N. Chicago, IL, 60064, USA

    Thomas Hudzik

  3. International Neuropsychiatry Consultants, Highland Park, IL, 60035, USA

    Marion E. Wolf

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  1. Aron D. Mosnaim
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  2. Thomas Hudzik
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  3. Marion E. Wolf
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Correspondence to Aron D. Mosnaim.

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Mosnaim, A.D., Hudzik, T. & Wolf, M.E. Analgesic Effects of β-Phenylethylamine and Various Methylated Derivatives in Mice. Neurochem Res 39, 1675–1680 (2014). https://doi.org/10.1007/s11064-014-1354-7

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