substituted mescaline analogue

{{Short description|Class of chemical compounds}}

File:Mescaline Structural Formulae bondline.svg.]]

A substituted mescaline analogue, also known as a scaline and typically but not always a 4-substituted 3,5-dimethoxyphenethylamine, is an analogue of the phenethylamine serotonergic psychedelic mescaline (3,4,5-trimethoxyphenethylamine).{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6 | access-date=1 February 2025}}{{cite journal | vauthors = Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT | title = Mescaline analogs: substitutions at the 4-position | journal = NIDA Res Monogr | volume = | issue = 22 | pages = 27–37 | date = 1978 | pmid = 101882 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph22.pdf#page=38 }}{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 74–91 | date = 1994 | pmid = 8742795 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 }}{{cite book | veditors = Iversen LL, Iversen SD, Snyder SH | last=Shulgin | first=Alexander T. | title=Stimulants | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333 | chapter-url=https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 | url=https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261 }}{{cite journal | vauthors = Shulgin AT | title = Mescaline: the chemistry and pharmacology of its analogs | journal = Lloydia | volume = 36 | issue = 1 | pages = 46–58 | date = March 1973 | pmid = 4576313 | doi = | url = https://bitnest.netfirms.com/external/Lloydia/36.1.46}}{{cite book | author1 = Alexander T. Shulgin | author2 = Ann Shulgin | title = PiHKAL: A Chemical Love Story | date = 1991 | publisher = Transform Press | edition = 1st | location = Berkeley, CA | isbn = 978-0-9630096-0-9 | oclc = 25627628 | url = https://books.google.com/books?id=O8AdHBGybpcC }}{{cite book | vauthors = Shulgin A, Manning T, Daley PF | title = The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher = Transform Press | location = Berkeley, CA | volume = 1 | year = 2011 | isbn = 978-0-9630096-3-0 | oclc = 709667010 }}

Other related compounds include the 2C (4-substituted 2,5-dimethoxyphenethylamine) and DOx (4-substituted 2,5-dimethoxyamphetamine) compounds as well as 3,4,5-trimethoxyamphetamine (TMA) and other 4-substituted 3,5-dimethoxyamphetamines (3C drugs). They are also mescaline analogues, but the 2C and DOx drugs have a third methoxy group in the 2 position instead of the 3 position while TMA is an amphetamine rather than a phenethylamine.

The pharmacology of mescaline analogues has been studied.{{cite journal | vauthors = Kolaczynska KE, Luethi D, Trachsel D, Hoener MC, Liechti ME | title = Receptor Interaction Profiles of 4-Alkoxy-3,5-Dimethoxy-Phenethylamines (Mescaline Derivatives) and Related Amphetamines | journal = Front Pharmacol | volume = 12 | issue = | pages = 794254 | date = 2021 | pmid = 35222010 | pmc = 8865417 | doi = 10.3389/fphar.2021.794254 | doi-access = free | url = }}{{cite journal | vauthors = Halberstadt AL, Chatha M, Chapman SJ, Brandt SD | title = Comparison of the behavioral effects of mescaline analogs using the head twitch response in mice | journal = J Psychopharmacol | volume = 33 | issue = 3 | pages = 406–414 | date = March 2019 | pmid = 30789291 | pmc = 6848748 | doi = 10.1177/0269881119826610 | url = }} Mescaline analogues, or 4-substituted 3,5-dimethoxyphenethylamines specifically, tend to be much less potent than the 2C and DOx drugs. This relates to the fact that the 2,4,5-substitution pattern tends to be optimal in terms of receptor affinity and potency.{{cite journal | vauthors = Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, Glennon RA | title = 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists | journal = Journal of Medicinal Chemistry | volume = 43 | issue = 16 | pages = 3074–3084 | date = August 2000 | pmid = 10956215 | doi = 10.1021/jm9906062 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ad45346022bb7e6e1bec1fbfbcca3bcb60b13058 }} However, mescaline analogues are not infrequently much more potent than mescaline.

Substituted mescaline analogues have been extensively characterized by Alexander Shulgin and described in his books such as PiHKAL (Phenethylamines I Have Known and Loved) and The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds as well as in his literature reviews. They have also been studied by David E. Nichols{{cite journal | vauthors = Nichols DE, Dyer DC | title = Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogues | journal = J Med Chem | volume = 20 | issue = 2 | pages = 299–301 | date = February 1977 | pmid = 836502 | doi = 10.1021/jm00212a022 | url = }}{{cite journal | vauthors = Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, Nichols DE | title = Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives | journal = J Med Chem | volume = 40 | issue = 19 | pages = 2997–3008 | date = September 1997 | pmid = 9301661 | doi = 10.1021/jm970219x | url = }}{{cite journal | vauthors = McLean TH, Chambers JJ, Parrish JC, Braden MR, Marona-Lewicka D, Kurrasch-Orbaugh D, Nichols DE | title = C-(4,5,6-trimethoxyindan-1-yl)methanamine: a mescaline analogue designed using a homology model of the 5-HT2A receptor | journal = J Med Chem | volume = 49 | issue = 14 | pages = 4269–4274 | date = July 2006 | pmid = 16821786 | doi = 10.1021/jm060272y | url = }} and Daniel Trachsel,{{cite book | last1=Trachsel | first1=D. | last2=Lehmann | first2=D. | last3=Enzensperger | first3=C. | title=Phenethylamine: von der Struktur zur Funktion | trans-title = Phenethylamines: From Structure to Function | edition = 1 | publisher=Nachtschatten-Verlag | location = Solothurn | series=Nachtschatten-Science | year=2013 | isbn=978-3-03788-700-4 | oclc = 858805226 | url=https://books.google.com/books?id=-Us1kgEACAAJ | language=de | access-date=31 January 2025 }}{{cite journal | vauthors=Stoeckmann OV, Trachsel D, Liechti ME, Rudin D | title=Supplementum 276: Abstracts of the of the 8th Annual Spring Congress of the Swiss Society of General Internal Medicine: P181. New Mescaline Derivatives: Profiling of Scalines' Potency and Affinity on Different Serotonin Receptor Subtypes | journal=Swiss Medical Weekly | volume=154 | issue=5 | date=21 May 2024 | issn=1424-3997 | doi=10.57187/s.3896 | doi-access=free | pages=138S }} among other researchers.