2-Naphthylmethcathinone

Substituted cathinone stimulant drug BMAPN Bk-methamnetamine.svg skin-invert-image PSA NpSG 14 15 1 1 2-(methylamino)-1-(naphthalene-2-yl) propan-1-one 109453-73-8 65998790 112704365 DL8RX8N8NK BMAPN; βk-Methamnetamine CC(C(=O)C1=CC2=CC=CC=C2C=C1)NC 1S/C14H15NO/c1-10(15-2)14(16)13-8-7-11-5-3-4-6-12(11)9-13/h3-10,15H,1-2H3 QIMNQDXLKHGANJ-UHFFFAOYSA-N 2-Naphthylmethcathinone (BMAPN), also known as βk-methamnetamine, is a stimulant drug of the cathinone and naphthylaminopropane families. It inhibits dopamine reuptake and has rewarding and reinforcing properties in animal studies. Botanas CJ, Yoon SS, de la Peña JB, Dela Peña IJ, Kim M, Woo T, Seo JW, Jang CG, Park KT, Lee YH, Lee YS, Kim HJ, Cheong JH A novel synthetic cathinone, 2-(methylamino)-1-(naphthalen-2-yl) propan-1-one (BMAPN), produced rewarding effects and altered striatal dopamine-related gene expression in mice Behavioural Brain Research 317 494–501 January 2017 27737791 10.1016/j.bbr.2016.10.016 3095092 Simmons SJ, Kim E, Gentile TA, Murad A, Muschamp JW, Rawls SM 2018 Behavioral Profiles and Underlying Transmitters/Circuits of Cathinone-Derived Psychostimulant Drugs of Abuse. Zawilska J Synthetic Cathinones Current Topics in Neurotoxicity 12 125–152 Springer Cham 10.1007/978-3-319-78707-7_8 978-3-319-78706-0 It is banned under drug analogue legislation in a number of jurisdictions. The drug was at one point marketed under the name NRG-3, although only a minority of samples of substances sold under this name have been found to actually contain BMAPN, with most such samples containing mixtures of other cathinone derivatives. Brandt SD, Freeman S, Sumnall HR, Measham F, Cole J Analysis of NRG 'legal highs' in the UK: identification and formation of novel cathinones Drug Testing and Analysis 3 9 569–75 September 2011 21960541 10.1002/dta.204 Eiden C, Mathieu O, Cathala P, Debruyne D, Baccino E, Petit P, Peyriere H Toxicity and death following recreational use of 2-pyrrolidino valerophenone Clinical Toxicology Philadelphia, Pa. 51 9 899–903 November 2013 24111554 10.3109/15563650.2013.847187 22826544 + Monoamine release of BMAPN and related agents (EC50 Half maximal effective concentration, nM) Compound NE Norepinephrine DA Dopamine 5-HT Serotonin Ref d-Amphetamine 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 Glennon RA, Dukat M Neuropharmacology of New Psychoactive Substances (NPS) Structure-Activity Relationships of Synthetic Cathinones Current Topics in Behavioral Neurosciences 32 19–47 2017 Springer 27830576 5818155 10.1007/7854_2016_41 978-3-319-52442-9 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. Naphthylaminopropane (NAP; PAL-287) 11.1 12.6 3.4 Rothman RB, Blough BE, Woolverton WL, Anderson KG, Negus SS, Mello NK, Roth BL, Baumann MH Development of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration The Journal of Pharmacology and Experimental Therapeutics 313 3 1361–1369 June 2005 15761112 10.1124/jpet.104.082503 19802702 d-Methamphetamine 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 Methylnaphthylaminopropane (MNAP; PAL-1046) 34 10 13 Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters J Pharmacol Exp Ther 341 1 251–262 April 2012 22271821 3364510 10.1124/jpet.111.188946 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 l-Methcathinone 13.1 14.8 1,772 Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates The Journal of Pharmacology and Experimental Therapeutics 307 1 138–145 October 2003 12954796 10.1124/jpet.103.053975 19015584 2-Naphthylmethcathinone (BMAPN; βk-MNAP) 94% at 10μM 34 27 Blough BE, Decker AM, Landavazo A, Namjoshi OA, Partilla JS, Baumann MH, Rothman RB The dopamine, serotonin and norepinephrine releasing activities of a series of methcathinone analogs in male rat brain synaptosomes Psychopharmacology (Berl) 236 3 915–924 March 2019 30341459 6475490 10.1007/s00213-018-5063-9 Yadav Barkha J Understanding Structure–Activity Relationship of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate VCU Scholars Compass 16 July 2019 10.25772/MJQW-8C64 https://scholarscompass.vcu.edu/etd/5955/ 24 November 2024 d-Ethylamphetamine 28.8 44.1 333.0 Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones Neuropharmacology 245 109827 March 2024 38154512 10.1016/j.neuropharm.2023.109827 10842458 Nicole Lauren In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones 2022 ProQuest https://www.proquest.com/openview/a207e98868b4a9c5ac9296fb24abbcd8/ 5 December 2024 FIGURE 2-6: Release: Effects of the specified test drug on monoamine release by DAT (red circles), NET (blue squares), and SERT (black traingles) in rat brain tissue. [...] EC50 values determined for the drug indicated within the panel. [...] Ethylnaphthylaminopropane (ENAP; PAL-1045) 137 46 a 12 a Phenmetrazine 29–50.4 70–131 7,765–>10,000 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 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 Naphthylmetrazine (PAL-704) 203 111 RI Reuptake inhibitor (105) 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. Footnotes: a ENAP Ethylnaphthylaminopropane is a partial releaser of serotonin (Emax maximal efficacy = 66%) and dopamine (Emax maximal efficacy = 78%). 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 Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs Annals of the New York Academy of Sciences 1074 1 245–260 August 2006 17105921 10.1196/annals.1369.064 2006NYASA1074..245R 19739692 See also 1-Naphthylmethcathinone (AMAPN) βk-Ephenidine Methamnetamine Methylnaphthidate Methylone Naphyrone WF-23 References Category:Cathinones Category:Designer drugs Category:Methamphetamines Category:2-Naphthyl compounds Category:Naphthylethylamines Category:Serotonin-norepinephrine-dopamine releasing agents