2-Phenylmorpholine

vanc 6 2-Phenylmorpholine structure.svg skin-invert-image 200px Norepinephrine–dopamine releasing agent; Psychostimulant 23972-41-0 correct CAS 91101 82261 4069068 PAL-632; PAL632 2-phenylmorpholine 10 13 1 1 C1COC(CN1)C2=CC=CC=C2 1S/C10H13NO/c1-2-4-9(5-3-1)10-8-11-6-7-12-10/h1-5,10-11H,6-8H2 ZLNGFYDJXZZFJP-UHFFFAOYSA-N 2-Phenylmorpholine (code name PAL-632) is the parent compound of the substituted phenylmorpholine class of compounds. Meher CP, Purohit D, Kumar A, Singh R, Dubey A An Updated Review on Morpholine Derivatives With Their Pharmacological Actions International Journal of Health Sciences 13 April 2022 2550-696X 10.53730/ijhs.v6nS3.5983 free 2218–2249 https://sciencescholar.us/journal/index.php/ijhs/article/download/5983/2154 10 January 2025 Examples of 2-phenylmorpholine derivatives (i.e., substituted phenylmorpholines) include phenmetrazine (3-methyl-2-phenylmorpholine), phendimetrazine ((2S,3S)-3,4-dimethyl-2-phenylmorpholine), and pseudophenmetrazine ((2RS,3SR)-3-methyl-2-phenylmorpholine), which are monoamine releasing agents (MRAs) and psychostimulants. 2-Phenylmorpholine itself is a potent norepinephrine–dopamine releasing agent (NDRA) and hence may act as a stimulant similarly. + Monoamine release of 2-phenylmorpholine and related agents (EC50 Half maximal effective concentration, nM) Compound NE Norepinephrine DA Dopamine 5-HT Serotonin Ref Phenethylamine 10.9 39.5 >10,000 Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter Drug Alcohol Depend 147 1–19 February 2015 25548026 4297708 10.1016/j.drugalcdep.2014.12.005 Forsyth AN Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines ScholarWorks@UNO 22 May 2012 https://scholarworks.uno.edu/td/1436/ 4 November 2024 Dextroamphetamine 6.6–10.2 5.8–24.8 698–1,765 Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin Synapse 39 1 32–41 January 2001 11071707 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 15573624 Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products Neuropsychopharmacology 38 4 552–562 March 2013 23072836 3572453 10.1038/npp.2012.204 Blough B Dopamine-releasing agents Trudell ML, Izenwasser S Dopamine Transporters: Chemistry, Biology and Pharmacology 305–320 July 2008 978-0-470-11790-3 181862653 OL18589888W Wiley Hoboken [NJ] https://books.google.com/books?id=QCagLAAACAAJ https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf Partilla JS, Dersch CM, Baumann MH, Carroll FI, Rothman RB Profiling CNS Stimulants with a High-Throughput Assay for Biogenic Amine Transporter Substrates Problems of Drug Dependence 1999: Proceedings of the 61st Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc NIDA Res Monogr 180 1–476 (252) 1999 11680410 https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 https://web.archive.org/web/20230805004105/https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 dead August 5, 2023 RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). Phentermine released all three biogenic amines with an order of potency NE (IC50 = 28.8 nM)> DA (IC50 = 262 nM)> 5-HT (IC50 = 2575 nM). Aminorex released NE (IC50 = 26.4 nM), DA (IC50 = 44.8 nM) and 5-HT (IC50 = 193 nM). Chlorphentermine was a very potent 5-HT releaser (IC50 = 18.2 nM), a weaker DA releaser (IC50 = 935 nM) and inactive in the NE release assay. Chlorphentermine was a moderate potency inhibitor of [3H]NE uptake (Ki = 451 nM). Diethylpropion, which is self-administered, was a weak DA uptake inhibitor (Ki = 15 µM) and NE uptake inhibitor (Ki = 18.1 µM) and essentially inactive in the other assays. Phendimetrazine, which is self-administered, was a weak DA uptake inhibitor (IC50 = 19 µM), a weak NE uptake inhibitor (8.3 µM) and essentially inactive in the other assays. Dextromethamphetamine 12.3–14.3 8.5–40.4 736–1,292 Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue Neuropsychopharmacology 37 5 1192–1203 April 2012 22169943 3306880 10.1038/npp.2011.304 2-Phenylmorpholine 79 86 20,260 Phenmetrazine 29–50.4 70–131 7,765–>10,000 McLaughlin G, Baumann MH, Kavanagh PV, Morris N, Power JD, Dowling G, Twamley B, O'Brien J, Hessman G, Westphal F, Walther D, Brandt SD Synthesis, analytical characterization, and monoamine transporter activity of the new psychoactive substance 4-methylphenmetrazine (4-MPM), with differentiation from its ortho- and meta- positional isomers Drug Test Anal 10 9 1404–1416 September 2018 29673128 7316143 10.1002/dta.2396 Phenylmorpholines and analogues thereof Google Patents 20 May 2011 https://patents.google.com/patent/WO2011146850A1/en 7 December 2024 Phendimetrazine >10,000 >10,000 >100,000 Rothman RB, Katsnelson M, Vu N, Partilla JS, Dersch CM, Blough BE, Baumann MH Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain European Journal of Pharmacology 447 1 51–57 June 2002 12106802 10.1016/s0014-2999(02)01830-7 Pseudophenmetrazine 514 >10,000 (RI Reuptake inhibitor) >10,000 Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs: Rothman RB, Baumann MH Monoamine transporters and psychostimulant drugs European Journal of Pharmacology 479 1–3 23–40 October 2003 14612135 10.1016/j.ejphar.2003.08.054 Rothman RB, Baumann MH Therapeutic potential of monoamine transporter substrates Current Topics in Medicinal Chemistry 6 17 1845–1859 2006 17017961 10.2174/156802606778249766 http://www.bentham-direct.org/pages/content.php?CTMC/2006/00000006/00000017/0004R.SGM 5 May 2020 usurped https://web.archive.org/web/20170326103021/http://www.bentham-direct.org/pages/content.php?CTMC%2F2006%2F00000006%2F00000017%2F0004R.SGM 26 March 2017 subscription References Category:Norepinephrine-dopamine releasing agents Category:Phenylethanolamines Category:Phenylmorpholines Category:Stimulants