Naphthylaminopropane

{{Short description|Chemical compound}} {{distinguish|1-Naphthylaminopropane}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | IUPAC_name = 1-(Naphthalen-2-yl)propan-2-amine | image = Naphthylaminopropane.svg | image_class = skin-invert-image | width = 250px

| tradename = | pregnancy_category = | legal_status = Uncontrolled | routes_of_administration = Oral

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 18085-03-5 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 53PF675WUK | ATC_prefix = None | ATC_suffix = | PubChem = 10219723 | ChemSpiderID = 8395215 | ChEMBL = 471839 | synonyms = NAP; Naphthylisopropylamine; NIPA; PAL-287; Naphetamine; Amnetamine; 1-(2-Naphthyl)-2-aminopropane; beta-Methylnapthylethylamine; β-Methylnaphthylethylamine; 1-(β-Naphthyl)-2-aminopropane

| C=13 | H=15 | N=1 | SMILES = CC(N)Cc2ccc1ccccc1c2 | StdInChI=1S/C13H15N/c1-10(14)8-11-6-7-12-4-2-3-5-13(12)9-11/h2-7,9-10H,8,14H2,1H3 | StdInChIKey = UPQSZFKXKRKCGZ-UHFFFAOYSA-N }}

'''Naphthylaminopropane''' ('''NAP'''; code name '''PAL-287'''), also known as '''naphthylisopropylamine''' ('''NIPA'''), is an experimental drug of the amphetamine and naphthylaminopropane families that was under investigation for the treatment of alcohol and stimulant addiction.<ref name="RothmanBloughBaumann2006">{{cite journal | vauthors = Rothman RB, Blough BE, Baumann MH | title = Dual dopamine-5-HT releasers: potential treatment agents for cocaine addiction | journal = Trends Pharmacol Sci | volume = 27 | issue = 12 | pages = 612–618 | date = December 2006 | pmid = 17056126 | doi = 10.1016/j.tips.2006.10.006 | url = }}</ref><ref name="RothmanBloughBaumann2007">{{cite journal | vauthors = Rothman RB, Blough BE, Baumann MH | title = Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions | journal = The AAPS Journal | volume = 9 | issue = 1 | pages = E1-10 | date = January 2007 | pmid = 17408232 | pmc = 2751297 | doi = 10.1208/aapsj0901001 }}</ref>

==Pharmacology== ===Pharmacodynamics=== ====Activities==== Naphthylaminopropane is a serotonin–norepinephrine–dopamine releasing agent (SNDRA).<ref name="WeeAndersonBaumann2005" /><ref name="RothmanBloughWoolverton2005" /> Its {{Abbrlink|EC50|half-maximal effective concentration}} values for induction of monoamine release are 3.4{{nbsp}}nM for serotonin, 11.1{{nbsp}}nM for norepinephrine, and 12.6{{nbsp}}nM for dopamine.<ref name="WeeAndersonBaumann2005">{{cite journal | vauthors = Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL | title = Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 313 | issue = 2 | pages = 848–854 | date = May 2005 | pmid = 15677348 | doi = 10.1124/jpet.104.080101 | s2cid = 12135483 }}</ref><ref name="RothmanBloughWoolverton2005">{{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 = The Journal of Pharmacology and Experimental Therapeutics | volume = 313 | issue = 3 | pages = 1361–1369 | date = June 2005 | pmid = 15761112 | doi = 10.1124/jpet.104.082503 | s2cid = 19802702 }}</ref>

The drug is also an agonist of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors.<ref name="RothmanBloughBaumann2007" /> Its {{Abbr|EC50|half-maximal effective concentration}} values are 466{{nbsp}}nM at the serotonin 5-HT2A receptor, 40{{nbsp}}nM at the serotonin 5-HT2B receptor, and 2.3{{nbsp}}nM at the serotonin 5-HT2C receptor.<ref name="RothmanBloughBaumann2007" /> It is a full agonist of the serotonin 5-HT2A and 5-HT2B receptors and a weak partial agonist of the serotonin 5-HT2C receptor ({{Abbrlink|Emax|maximal efficacy}} = 20%).<ref name="RothmanBloughBaumann2006" /><ref name="RothmanBloughBaumann2007" />

Naphthylaminopropane has been found to act as a potent monoamine oxidase A (MAO-A) inhibitor, with an {{Abbrlink|IC50|half-maximal inhibitory concentration}} of 420{{nbsp}}nM.<ref name="Reyes-ParadaIturriaga-VasquezCassels2019">{{cite journal | vauthors = Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK | title = Amphetamine Derivatives as Monoamine Oxidase Inhibitors | journal = Front Pharmacol | volume = 10 | issue = | article-number = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free | url = }}</ref><ref name="Vilches-HerreraMiranda-SepúlvedaRebolledo-Fuentes2009">{{cite journal | vauthors = Vilches-Herrera M, Miranda-Sepúlveda J, Rebolledo-Fuentes M, Fierro A, Lühr S, Iturriaga-Vasquez P, Cassels BK, Reyes-Parada M | title = Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors | journal = Bioorg Med Chem | volume = 17 | issue = 6 | pages = 2452–2460 | date = March 2009 | pmid = 19243954 | doi = 10.1016/j.bmc.2009.01.074 | url = http://americanae.aecid.es/americanae/es/registros/registro.do?tipoRegistro=MTD&idBib=3268134}}</ref> This is similar to the potency of the well-known MAO-A inhibitors ''para''-methoxyamphetamine (PMA) and 4-methylthioamphetamine (4-MTA).<ref name="Reyes-ParadaIturriaga-VasquezCassels2019" />

{| class="wikitable" style="font-size:small;" |+ {{Nowrap|Monoamine release of naphthylaminopropane 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 || <ref name="RothmanBaumannDersch2001">{{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 }}</ref><ref name="BaumannPartillaLehner2013">{{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 }}</ref><ref name="Blough2008">{{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 }}</ref><ref name="GlennonDukat2017">{{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 = }}</ref><ref name="PartillaDerschBaumann1999">{{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 Substrates | 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 | archive-url = https://web.archive.org/web/20230805004105/https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 | url-status = dead | archive-date = August 5, 2023 | 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.}}</ref> |- | Naphthylaminopropane (NAP; PAL-287) || 11.1 || 12.6 || 3.4 || <ref name="RothmanBloughWoolverton2005"/><ref name="Blough2008" /> |- | ''d''-Methamphetamine || 12.3–14.3 || 8.5–40.4 || 736–1,292 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{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 }}</ref><ref name="Blough2008" /><ref name="PartillaDerschBaumann1999" /> |- | Methylnaphthylaminopropane (MNAP; PAL-1046) || 34 || 10 || 13 || <ref name="RothmanPartillaBaumann2012" /><ref name="ReithBloughHong2015" /> |- | ''l''-Methcathinone || 13.1 || 14.8 || 1,772 || <ref name="RothmanVuPartilla2003">{{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 }}</ref><ref name="GlennonDukat2017" /> |- | 2-Naphthylmethcathinone (BMAPN; βk-MNAP) || 94% at 10{{nbsp}}μM || 34 || 27 || <ref name="BloughDeckerLandavazo2019" /><ref name="Yadav2019">{{cite thesis | last=Yadav | first=Barkha J | title=Understanding Structure–Activity Relationship of Synthetic Cathinones (Bath Salts) Utilizing Methylphenidate | website=VCU Scholars Compass | date=16 July 2019 | doi=10.25772/MJQW-8C64 | url=https://scholarscompass.vcu.edu/etd/5955/ | access-date=24 November 2024 }}</ref> |- | ''d''-Ethylamphetamine || 28.8 || 44.1 || 333.0 || <ref name="FitzgeraldGannonWalther2024">{{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 = | article-number = 109827 | date = March 2024 | pmid = 38154512 | doi = 10.1016/j.neuropharm.2023.109827 | pmc = 10842458 | url = }}</ref><ref name="Nicole2022">{{cite web | last=Nicole | first=Lauren | title=In vivo Structure-Activity Relationships of Substituted Amphetamines and Substituted Cathinones | date=2022 | website=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. [...]}}</ref> |- | Ethylnaphthylaminopropane (ENAP; PAL-1045) || 137 || 46 a || 12 a || <ref name="RothmanPartillaBaumann2012" /> |- | Phenmetrazine || 29–50.4 || 70–131 || 7,765–>10,000 || <ref name="RothmanKatsnelsonVu2002">{{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 }}</ref><ref name="Blough2008" /><ref name="McLaughlinBaumannKavanagh2018">{{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 = }}</ref><ref name="WO2011146850A1">{{cite web | title=Phenylmorpholines and analogues thereof | website=Google Patents | date=20 May 2011 | url=https://patents.google.com/patent/WO2011146850A1/en | access-date=7 December 2024}}</ref> |- | Naphthylmetrazine (PAL-704) || 203 || 111 || {{Abbr|RI|Reuptake inhibitor}} (105) || <ref name="WO2011146850A1" /> |- | colspan="5" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; 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:'''<ref name="RothmanBaumann2003">{{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 }}</ref><ref name="RothmanBaumann2006" /> |}

====Effects==== In animal studies, naphthylaminopropane was shown to reduce cocaine self-administration, yet produced relatively weak stimulant effects when administered alone, being a much less effective stimulant than dextroamphetamine.<ref name="RothmanBloughWoolverton2005" /><ref name="Mehes1952">{{cite journal | vauthors = Mehes G | title = Uber die pharmakologische wirkung vom 1-(alpha-naphtyl)-, beziehungsweise 1-(beta-naphtyl)-2-aminopropan; Beiträge zum Zuzammenhang zwischen chemischer Struktur und Wirkung | trans-title = On the pharmacological effects of 1-(alpha-naphthyl)-, and 1-(beta-naphthyl)-2-aminopropane; a contribution on the problem of chemical structure and effect | journal = Acta Physiologica Academiae Scientiarum Hungaricae | volume = 3 | issue = 1 | pages = 137–151 | year = 1952 | pmid = 13050439 }}</ref><ref name="GlennonYoungHauck1984">{{cite journal | vauthors = Glennon RA, Young R, Hauck AE, McKenney JD | title = Structure-activity studies on amphetamine analogs using drug discrimination methodology | journal = Pharmacology, Biochemistry, and Behavior | volume = 21 | issue = 6 | pages = 895–901 | date = December 1984 | pmid = 6522418 | doi = 10.1016/S0091-3057(84)80071-4 | s2cid = 36455297 }}</ref> Further research was being conducted in primates to see if the drug would be a useful substitute for treating drug addiction in humans.<ref name="NegusMelloBlough2007">{{cite journal | vauthors = Negus SS, Mello NK, Blough BE, Baumann MH, Rothman RB | title = Monoamine releasers with varying selectivity for dopamine/norepinephrine versus serotonin release as candidate "agonist" medications for cocaine dependence: studies in assays of cocaine discrimination and cocaine self-administration in rhesus monkeys | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 320 | issue = 2 | pages = 627–636 | date = February 2007 | pmid = 17071819 | doi = 10.1124/jpet.106.107383 | s2cid = 8326027 }}</ref>

An important observation is that in behavioral studies, rodents would consistently self-administer selective norepinephrine–dopamine releasing agents (NDRAs) like dextroamphetamine, yet compounds that also potently release serotonin like naphthylaminopropane would not be self-administered.<ref name="RothmanBloughWoolverton2005" /> In addition to the drug's effects on self-administration, the available evidence suggests that the locomotor activation caused by dopamine releasers is also dampened when they additionally induce serotonin release.<ref name="RothmanBaumann2006">{{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 }}</ref> Notably, despite potent dopamine release induction, naphthylaminopropane produces weak or no locomotor activation in rodents.<ref name="RothmanBloughBaumann2006" />

The high affinity of naphthylaminopropane for the serotonin 5-HT2C receptor meant that it might function as an appetite suppressant and was being considered for possible clinical use for this indication (i.e., weight loss). However, concerns were raised over the affinity of the drug for the serotonin 5-HT2B receptor, since some of the more serious side effects of the serotonin-releasing weight loss drug fenfluramine were linked to activation of this receptor.<ref name="RothmanBaumann2009">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Serotonergic drugs and valvular heart disease | journal = Expert Opinion on Drug Safety | volume = 8 | issue = 3 | pages = 317–329 | date = May 2009 | pmid = 19505264 | pmc = 2695569 | doi = 10.1517/14740330902931524 }}</ref> It is uncertain, although was considered unlikely per the researchers who developed the drug, that activation of the serotonin 5-HT2A and 5-HT2B receptors occurs to a significant degree ''in vivo''.<ref name="RothmanBloughBaumann2006" />

==Chemistry== Naphthylaminopropane was first described in the scientific literature by 1939.<ref name="BlickeMaxwell1939">{{cite journal | vauthors = Blicke FF, Maxwell CE | title=Naphthylaminoalkanes | journal=Journal of the American Chemical Society | volume=61 | issue=7 | date=1939 | issn=0002-7863 | doi=10.1021/ja01876a039 | pages=1780–1782| bibcode=1939JAChS..61.1780B }}</ref><ref name="Mehes1952" /> The drug is also known as 2-naphthylaminopropane (2-NAP) or β-naphthylaminopropane, and it was described along with its positional isomer 1-naphthylaminopropane (1-NAP; α-naphthylaminopropane).<ref name="GlennonYoungHauck1984" /><ref name="Mehes1952" /> Both 2-NAP and 1-NAP failed to substitute for dextroamphetamine in rodent drug discrimination tests, suggesting that they lack psychostimulant-like effects.<ref name="GlennonYoungHauck1984" /> The β-keto and ''N''-methyl analogue of 2-NAP has been assessed and was found to act as a potent SNDRA similarly to naphthylaminopropane.<ref name="BloughDeckerLandavazo2019">{{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 = }}</ref>

Naphthylaminopropane is structurally related to certain rigid analogues of amphetamine.<ref name="GlennonYoungHauck1984" /> Rigid amphetamine analogues include 2-aminotetralin (2-AT), 2-amino-1,2-dihydronaphthalene (2-ADN), 1-phenylpiperazine (1-PP), 2-aminoindane (2-AI), {{Abbrlink|6-AB|6-amino-6,7,8,9-tetrahydro-5H-benzocycloheptene}}, and {{Abbrlink|7-AB|7-amino-6,7,8,9-tetrahydro-5H-benzocycloheptene}}.<ref name="GlennonYoungHauck1984" /><ref name="OberlenderNichols1991">{{cite journal | vauthors = Oberlender R, Nichols DE | s2cid = 19069907 | title = Structural variation and (+)-amphetamine-like discriminative stimulus properties | journal = Pharmacology, Biochemistry, and Behavior | volume = 38 | issue = 3 | pages = 581–586 | date = March 1991 | pmid = 2068194 | doi = 10.1016/0091-3057(91)90017-V | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=77437efa02b4a0f688e4038b153ddfafde6da614| url-access = subscription }}</ref><ref name="HathawayNicholsYim1982">{{cite journal |vauthors=Hathaway BA, Nichols DE, Nichols MB, Yim GK | title = A new, potent, conformationally restricted analogue of amphetamine: 2-amino-1,2-dihydronaphthalene | journal = Journal of Medicinal Chemistry | volume = 25 | issue = 5 | pages = 535–538 |date=May 1982 | pmid = 6123601 | doi = 10.1021/jm00347a011}}</ref>

A few derivatives of naphthylaminopropane have been developed or have appeared, including methamnetamine (''N''-methylnaphthylaminopropane; MNAP; PAL-1046), ''N''-ethylnaphthylaminopropane (ENAP; PAL-1045), and BMAPN (βk-methamnetamine; β-keto-MNAP; 2-naphthylmethcathinone).<ref name="RothmanPartillaBaumann2012">{{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 = }}</ref><ref name="ReithBloughHong2015">{{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 = }}</ref><ref name="BloughDeckerLandavazo2019" /><ref name="BotanasYoondelaPeña2017">{{cite journal | vauthors = 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 | title = 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 | journal = Behav Brain Res | volume = 317 | issue = | pages = 494–501 | date = January 2017 | pmid = 27737791 | doi = 10.1016/j.bbr.2016.10.016 | url = }}</ref> Like naphthylaminopropane, these derivatives also act as potent monoamine releasing agents, including of serotonin, norepinephrine, and/or dopamine.<ref name="RothmanPartillaBaumann2012" /><ref name="ReithBloughHong2015" /><ref name="BloughDeckerLandavazo2019" /><ref name="BotanasYoondelaPeña2017" />

== References == {{Reflist}}

{{Stimulants}} {{Monoamine releasing agents}} {{Serotonin receptor modulators}} {{Monoamine metabolism modulators}} {{Phenethylamines}} {{Chemical classes of psychoactive drugs}}

Category:5-HT2A agonists Category:5-HT2B agonists Category:5-HT2C agonists Category:Designer drugs Category:Entactogens Category:Monoamine oxidase inhibitors Category:2-Naphthyl compounds Category:Naphthylethylamines Category:Serotonin-norepinephrine-dopamine releasing agents Category:Stimulants Category:Substituted amphetamines