| Revision as of 10:57, 25 February 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL.← Previous edit |
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{{distinguish|amphetamine|β-Methylphenethylamine}} |
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{{Use dmy dates|date=October 2014}} |
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{{DISPLAYTITLE:''N''-Methylphenethylamine}} |
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{{chembox |
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{{chembox |
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| Name = ''N''-Methylphenethylamine |
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| verifiedrevid = 400309123 |
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| verifiedrevid = 415845541 |
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|Reference=<ref> at ]</ref> |
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| Reference = <ref> at ]</ref> |
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|ImageFile=Methylphenethylamine.png |
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| ImageFile = N-methylphenethylamine2DCSD.svg |
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|ImageSize=200px |
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| ImageFile2 = N-Methylphenethylamine molecule ball.png |
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|IUPACName=''N''-Methyl-2-phenylethanamine |
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| PIN = ''N''-Methyl-2-phenylethan-1-amine |
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|OtherNames=''N''-Methylphenethylamine |
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| OtherNames = ''N''-Methyl-2-phenylethanamine<br />''N''-Methylphenethylamine<br />''N''-Methyl-β-phenethylamine<br />"Nymphetamine" {{Citation needed|date=April 2024}} |
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|Section1= {{Chembox Identifiers |
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| Section1 = {{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 11019 |
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| ChemSpiderID = 11019 |
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| InChI = 1/C9H13N/c1-10-8-7-9-5-3-2-4-6-9/h2-6,10H,7-8H2,1H3 |
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| InChI = 1/C9H13N/c1-10-8-7-9-5-3-2-4-6-9/h2-6,10H,7-8H2,1H3 |
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| InChIKey = SASNBVQSOZSTPD-UHFFFAOYAA |
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| InChIKey = SASNBVQSOZSTPD-UHFFFAOYAA |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 45763 |
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| ChEMBL = 45763 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = SASNBVQSOZSTPD-UHFFFAOYSA-N |
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| StdInChIKey = SASNBVQSOZSTPD-UHFFFAOYSA-N |
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| CASNo=589-08-2 |
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| CASNo=589-08-2 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 02N4V81704 |
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| PubChem=11503 |
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| PubChem=11503 |
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| SMILES = N(CCc1ccccc1)C |
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| SMILES = CNCCc1ccccc1 |
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|Section2= {{Chembox Properties |
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| Section2 = {{Chembox Properties |
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| Formula=C<sub>9</sub>H<sub>13</sub>N |
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| C=9|H=13|N=1 |
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| Appearance=Colorless liquid |
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| MolarMass=135.21 g/mol |
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| Density=0.93 g/mL |
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| Appearance= |
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| MeltingPt= |
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| BoilingPtC=203 |
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| BoilingPtC=203 |
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|Section3= {{Chembox Hazards |
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| Section3 = {{Chembox Hazards |
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'''''N''-Methylphenethylamine''' ('''NMPEA''') is a ] ] in humans that is derived from the trace amine, ] (PEA).<ref name="Pendleton 263–8">{{cite journal | vauthors = Pendleton RG, Gessner G, Sawyer J | title = Studies on lung N-methyltransferases, a pharmacological approach | journal = Naunyn-Schmiedeberg's Arch. Pharmacol. | volume = 313 | issue = 3 | pages = 263–8 |date=September 1980 | pmid = 7432557 | doi = 10.1007/bf00505743| s2cid = 1015819 }}</ref><ref name="Trace Amines" /> It has been detected in human urine (<1 μg over 24 hours)<ref>G. P. Reynolds and D. O. Gray (1978) ''J. Chrom. B: Biomedical Applications'' '''145''' 137–140.</ref> and is produced by ] with ] as a substrate, which significantly increases PEA's effects.<ref name="Pendleton 263–8"/><ref name="Trace Amines" /> PEA breaks down into ] which is further broken down into ] by ]. When this is inhibited by ]s, it allows more of the PEA to be metabolized into nymphetamine (NMPEA) and not wasted on the weaker inactive metabolites. |
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'''Methylphenethylamine''' is a ] found in some ] trees. |
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PEA and NMPEA are both ] that are found in a number of different plant species as well.<ref>T. A. Smith (1977). "Phenethylamine and related compounds in plants." ''Phytochemistry'' '''16''' 9–18.</ref> Some '']'' species, such as '']'', contain remarkably high levels of NMPEA (~2300–5300 ppm).<ref>B. A. Clement, C. M. Goff and T. D. A. Forbes (1998) ''Phytochemistry'' '''49''' 1377–1380.</ref> NMPEA is also present at low concentrations (< 10 ppm) in a wide range of foodstuffs.<ref>G. B. Neurath et al. (1977) ''Fd. Cosmet. Toxicol.'' '''15''' 275–282.</ref> |
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== See also == |
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* ] |
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NMPEA is a ] of ].<ref name ="NMPH">{{cite journal | vauthors = Mosnaim AD, Callaghan OH, Hudzik T, Wolf ME | title = Rat brain-uptake index for phenylethylamine and various monomethylated derivatives | journal = Neurochem. Res. | volume = 38 | issue = 4 | pages = 842–6 |date=April 2013 | pmid = 23389662 | doi = 10.1007/s11064-013-0988-1 | s2cid = 18514146 }}</ref> |
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==References== |
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<references/> |
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==Biosynthesis== |
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{{Phenethylamines}} |
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{{Phenylalanine biosynthesis|caption= ''N''-methylphenethylamine, an ] in humans,<ref name="Trace Amines" /> is an isomer of amphetamine with the same ], ], a ] which modulates catecholamine neurotransmission.<ref name="Miller">{{cite journal | author = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = J. Neurochem. | volume = 116 | issue = 2 | pages = 164–176 |date=January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref>|align=left}}{{clear}} |
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==Chemistry== |
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] |
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In appearance, NMPEA is a colorless liquid. NMPEA is a ], with pK<sub>a</sub> = 10.14; pK<sub>b</sub> = 3.86 (calculated from data given as K<sub>b</sub><ref name = Car>W.H. Carothers, C. F. Bickford and G. J. Hurwitz (1927) ''J. Am. Chem. Soc.'' '''49''' 2908–2914.</ref>). It forms a hydrochloride salt, m.p. 162–164 °C.<ref>C. Z. Ding et al. (1993) ''J. Med. Chem.'' '''36''' 1711–1715.</ref> |
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Although NMPEA is available commercially, it may be synthesized by various methods. An early synthesis reported by Carothers and co-workers involved conversion of phenethylamine to its ''p''-toluenesulfonamide, followed by ''N''-methylation using ], then hydrolysis of the sulfonamide.<ref name = Car/> A more recent method, similar in principle, and used for making NMPEA radio-labeled with <sup>14</sup>C in the N-methyl group, started with the conversion of phenethylamine to its trifluoroacetamide. This was N-methylated (in this particular case using <sup>14</sup>C – labeled methyl iodide), and then the amide hydrolyzed.<ref>I. Osamu (1983) ''Eur. J. Nucl. Med.'' '''8''' 385–388.</ref> |
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NMPEA is a substrate for both ] (K<sub>M</sub> = 58.8 μM) and ] (K<sub>M</sub> = 4.13 μM) from rat brain mitochondria.<ref>O. Suzuki, M. Oya and Y. Katsumata (1980) ''Biochem. Pharmacol.'' '''29''' 2663–2667.</ref> |
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{{organic-compound-stub}} |
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==Pharmacology== |
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NMPEA is a ], with 1/350 x the potency of ].<ref>W. H. Hartung (1945) ''Ind. Eng. Chem.'' '''37''' 126–137.</ref> |
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Like its parent compound, PEA, and isomer, ], NMPEA is a potent ] of ] (hTAAR1).<ref name="Trace Amines">{{cite journal | author = Broadley KJ | title = The vascular effects of trace amines and amphetamines | journal = Pharmacol. Ther. | volume = 125 | issue = 3 | pages = 363–375 |date=March 2010 | pmid = 19948186 | doi = 10.1016/j.pharmthera.2009.11.005 | quote= '''Fig. 2.''' Synthetic and metabolic pathways for endogenous and exogenously administered trace amines and sympathomimetic amines ...<br /> Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2) ... It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone ...<br />Thus, MAO inhibitors potentiate the peripheral effects of indirectly acting sympathomimetic amines ... this potentiation occurs irrespective of whether the amine is a substrate for MAO. An α-methyl group on the side chain, as in amphetamine and ephedrine, renders the amine immune to deamination so that they are not metabolized in the gut. Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut ...<br /> Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life ...}}</ref><ref name="Renaissance GPCR">{{cite journal |vauthors=Lindemann L, Hoener MC |title=A renaissance in trace amines inspired by a novel GPCR family |journal=Trends Pharmacol. Sci. |volume=26 |issue=5 |pages=274–281 |date=May 2005 |pmid=15860375 |doi=10.1016/j.tips.2005.03.007 |quote=In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT) and phenylethanolamine N-methyltransferase (PNMT) to the corresponding secondary amines (e.g. synephrine , N-methylphenylethylamine and N-methyltyramine ), which display similar activities on TAAR1 (TA1) as their primary amine precursors.}}</ref> It has comparable ] and ] properties to that of phenethylamine, amphetamine, and other ]s in rats.<ref name ="NMPH" /> |
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As with PEA, NMPEA is metabolized relatively rapidly by ]s during ];<ref name="Trace Amines" /><ref name="Renaissance GPCR" /> both compounds are preferentially metabolized by ].<ref name="Trace Amines" /><ref name="Renaissance GPCR" /> |
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===Toxicology=== |
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The "minimum lethal dose" (mouse, i.p.) of the HCl salt of NMPEA is 203 mg/kg;<ref>A. M. Hjort (1934) ''J. Pharm. Exp. Ther.'' '''52''' 101–112.</ref> the LD<sub>50</sub> for oral administration to mice of the same salt is 685 mg/kg.<ref>C. M. Suter and A. W. Weston (1941) ''J. Am. Chem. Soc.'' '''63''' 602–605.</ref> |
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Acute toxicity studies on NMPEA show an LD<sub>50</sub> = 90 mg/kg, after intravenous administration to mice.<ref>A. M. Lands and J. I. Grant (1952). "The vasopressor action and toxicity of cyclohexylethylamine derivatives." ''J. Pharmacol. Exp. Ther.'' '''106''' 341–345.</ref> |
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== References == |
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{{Reflist}} |
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{{Amphetamine|state=expanded}} |
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{{Stimulants}} |
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{{Adrenergics}} |
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{{Dopaminergics}} |
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{{TAAR ligands}} |
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{{Phenethylamines}} |
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{{DEFAULTSORT:Methylphenethylamine, N-}} |
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