| synonyms = PAL-678; PAL678; 2-(2′-Naphthyl)morpholine; 2-(Naphthalen-2-yl)morpholine
| StdInChI = 1S/C14H15NO/c1-2-4-12-9-13(6-5-11(12)3-1)14-10-15-7-8-16-14/h1-6,9,14-15H,7-8,10H2
| class="wikitable" style="font-size:small;"
|+ {{Nowrap|Monoamine release of naphthylmorpholine and related agents ({{Abbrlink|EC50|Half maximal effective concentration}}, nM)}} |
| Compound | data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} | data-sort-type="number" | {{abbrlink|DA|Dopamine}} | data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} | Ref |
|---|
| d-Amphetamine | 6.6–10.2 | 5.8–24.8 | 698–1,765 | [{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | s2cid = 15573624 }}][{{cite journal | vauthors = 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 | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | date = March 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}][{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}][{{cite book | vauthors = Glennon RA, Dukat M | title = Neuropharmacology of New Psychoactive Substances (NPS) | chapter = Structure-Activity Relationships of Synthetic Cathinones | series = Current Topics in Behavioral Neurosciences | volume = 32 | pages = 19–47 | date = 2017 | publisher = Springer | pmid = 27830576 | pmc = 5818155 | doi = 10.1007/7854_2016_41 | isbn = 978-3-319-52442-9 | chapter-url = }}][{{cite book | vauthors = Partilla JS, Dersch CM, Baumann MH, Carroll FI, Rothman RB | chapter = Profiling CNS Stimulants with a High-Throughput Assay for Biogenic Amine Transporter Substractes | title = Problems of Drug Dependence 1999: Proceedings of the 61st Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc | series = NIDA Res Monogr | volume = 180 | pages = 1–476 (252) | date = 1999 | pmid = 11680410 | doi = | url = https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 | quote = 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 | [{{cite journal | vauthors = Rothman RB, Blough BE, Woolverton WL, Anderson KG, Negus SS, Mello NK, Roth BL, Baumann MH | title = Development of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration | journal = J Pharmacol Exp Ther | volume = 313 | issue = 3 | pages = 1361–1369 | date = June 2005 | pmid = 15761112 | doi = 10.1124/jpet.104.082503 | url = }}] |
| d-Methamphetamine | 12.3–14.3 | 8.5–40.4 | 736–1,292 | [{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | date = April 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}] |
| Methylnaphthylaminopropane (MNAP; PAL-1046) | 34 | 10 | 13 | [{{cite journal | vauthors = Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE | title = Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters | journal = J Pharmacol Exp Ther | volume = 341 | issue = 1 | pages = 251–262 | date = April 2012 | pmid = 22271821 | pmc = 3364510 | doi = 10.1124/jpet.111.188946 | url = }}][{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug Alcohol Depend | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 | url = }}] |
| l-Methcathinone | 13.1 | 14.8 | 1,772 | [{{cite journal | vauthors = Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA | title = In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 307 | issue = 1 | pages = 138–145 | date = October 2003 | pmid = 12954796 | doi = 10.1124/jpet.103.053975 | s2cid = 19015584 }}] |
| 2-Naphthylmethcathinone (BMAPN; βk-MNAP) | 94% at 10{{nbsp}}μM | 34 | 27 | [{{cite journal | vauthors = Blough BE, Decker AM, Landavazo A, Namjoshi OA, Partilla JS, Baumann MH, Rothman RB | title = The dopamine, serotonin and norepinephrine releasing activities of a series of methcathinone analogs in male rat brain synaptosomes | journal = Psychopharmacology (Berl) | volume = 236 | issue = 3 | pages = 915–924 | date = March 2019 | pmid = 30341459 | pmc = 6475490 | doi = 10.1007/s00213-018-5063-9 | url = }}][{{cite thesis | vauthors = Yadav BJ | title=Understanding Structure–Activity Relationship of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate | work=Theses and Dissertations | via = VCU Scholars Compass | publisher = Virginia Commonwealth University | date=16 July 2019 | doi=10.25772/MJQW-8C64 | url=https://scholarscompass.vcu.edu/etd/5955/ | access-date=24 November 2024 }}] |
| d-Ethylamphetamine | 28.8 | 44.1 | 333.0 | [{{cite journal | vauthors = Fitzgerald LR, Gannon BM, Walther D, Landavazo A, Hiranita T, Blough BE, Baumann MH, Fantegrossi WE | title = Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones | journal = Neuropharmacology | volume = 245 | issue = | pages = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = }}][{{cite thesis | vauthors = Nicole L | degree = Ph.D. | publisher = University of Arkansas for Medical Sciences | title=In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones | date=2022 | via = ProQuest | url=https://www.proquest.com/openview/a207e98868b4a9c5ac9296fb24abbcd8/ | access-date=5 December 2024 | quote = 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 | |
| 2-Phenylmorpholine (PAL-632) | 79 | 86 | 20,260 | |
| Naphthylmorpholine (PAL-678) | {{Nowrap|88% at 10{{nbsp}}μM}} | {{Nowrap|79% at 10{{nbsp}}μM}} | {{Nowrap|92% at 10{{nbsp}}μM}} | |
| Phenmetrazine | 29–50.4 | 70–131 | 7,765–>10,000 | [{{cite journal | vauthors = Rothman RB, Katsnelson M, Vu N, Partilla JS, Dersch CM, Blough BE, Baumann MH | title = Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain | journal = European Journal of Pharmacology | volume = 447 | issue = 1 | pages = 51–57 | date = June 2002 | pmid = 12106802 | doi = 10.1016/s0014-2999(02)01830-7 }}][{{cite journal | vauthors = 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 | title = 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 | journal = Drug Test Anal | volume = 10 | issue = 9 | pages = 1404–1416 | date = September 2018 | pmid = 29673128 | pmc = 7316143 | doi = 10.1002/dta.2396 | url = }}] |
| Naphthylmetrazine (PAL-704) | 203 | 111 | {{Abbr|RI|Reuptake inhibitor}} (105) | |
colspan="5" style="width: 1px; background-color:#eaecf0; text-align: center;" | 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 {{Abbrlink|ENAP|Ethylnaphthylaminopropane}} is a partial releaser of serotonin ({{Abbrlink|Emax|maximal efficacy}} = 66%) and dopamine ({{Abbr|Emax|maximal efficacy}} = 78%). Refs: [{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = European Journal of Pharmacology | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 }}][{{cite journal | vauthors = Rothman RB, Baumann MH | title = Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs | journal = Annals of the New York Academy of Sciences | volume = 1074 | issue = 1 | pages = 245–260 | date = August 2006 | pmid = 17105921 | doi = 10.1196/annals.1369.064 | bibcode = 2006NYASA1074..245R | s2cid = 19739692 }}] |