:Pellotine

{{Chembox

| ImageFile = Pellotine.svg

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| SystematicName = 6,7-Dimethoxy-1,2-dimethyl-3,4-dihydro-1H-isoquinolin-8-ol

| OtherNames = Peyotline; N-Methylanhalonidine; 8-Hydroxy-6,7-dimethoxy-1,2-dimethyl-1,2,3,4-tetrahydroisoquinoline

|Section1={{Chembox Identifiers

| CASNo = 83-14-7

| CASNo_Ref = {{cascite|correct|CAS}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 7RW0YY488A

| PubChem = 65742

| ChemSpiderID = 59165

| StdInChI = 1S/C13H19NO3/c1-8-11-9(5-6-14(8)2)7-10(16-3)13(17-4)12(11)15/h7-8,15H,5-6H2,1-4H3

| StdInChIKey = NKHMWHLJHODBEP-UHFFFAOYSA-N

| SMILES = CC1C2=C(C(=C(C=C2CCN1C)OC)OC)O}}

|Section2={{Chembox Properties

| C=13 | H=19 | N=1 | O=3

| Appearance =

| Density =

| MeltingPt = 110 to 113

| BoilingPt =

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|Section3={{Chembox Hazards

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| FlashPt =

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| LD50 = 10 mg/kg (intravenous, dog)

}} }}

Pellotine, also known as peyotline or N-methylanhalonidine, is a tetrahydroisoquinoline alkaloid found in Lophophora species, in particular L. diffusa.{{cite journal | vauthors = Doesburg-van Kleffens M, Zimmermann-Klemd AM, Gründemann C | title = An Overview on the Hallucinogenic Peyote and Its Alkaloid Mescaline: The Importance of Context, Ceremony and Culture | journal = Molecules | volume = 28 | issue = 24 | date = December 2023 | page = 7942 | pmid = 38138432 | pmc = 10746114 | doi = 10.3390/molecules28247942 | doi-access = free | url = }}{{cite journal|pmid=647075|year=1978|last1=Gabermann|first1=V|title=Estimation of mescaline and pellotine in Lophophora coulter plants (Cactaceae) by means of the oscillographic polarography|volume=43|issue=2|pages=246–51|journal=Biokhimiia (Moscow, Russia)}}{{cite journal |last1=Chan |first1=Camilla B. |last2=Poulie |first2=Christian B. M. |last3=Wismann |first3=Simon S. |last4=Soelberg |first4=Jens |last5=Kristensen |first5=Jesper L. |title=The Alkaloids from Lophophora diffusa and Other "False Peyotes" |journal=Journal of Natural Products |date=27 August 2021 |volume=84 |issue=8 |pages=2398–2407 |doi=10.1021/acs.jnatprod.1c00381|pmid=34264089 |bibcode=2021JNAtP..84.2398C |s2cid=235907705 }} It is the second most common alkaloid found in Lophophora williamsii (peyote). Pellotine is slightly sedative, and has been used by Native Americans as a constituent of peyote for sacramental purposes.{{Cite journal|title=The American Indian Church and its sacramental use of peyote: A review for professionals in the mental-health arena|journal = Mental Health, Religion & Culture|volume = 8|issue = 4|pages = 277–290|last=Jones|first=Peter|date=2007|doi=10.1080/13674670412331304348|s2cid = 144932041}} It was reportedly once marketed for use as a sedative.

Pharmacology and effects

Doses of 8 to 10{{nbsp}}mg of isolated pellotine are known to cause convulsions in frogs.{{cite journal |last1=Heffter |first1=Arthur |title=Ueber Pellote |journal=Archiv für Experimentelle Pathologie und Pharmakologie |date=1894 |volume=34 |issue=1–2 |pages=65–86 |doi=10.1007/bf01864855 |s2cid=28789116 |url=https://www.researchgate.net/publication/225876729}} When injected subcutaneously to humans, participants have reported drowsiness and a desire not to exert any physical or mental effort, with one study reporting it to have hypnotic effects. It is also reported to lower blood pressure and heart rate. Pellotine produced no hallucinogenic effects in humans at doses of up to 250{{nbsp}}mg.{{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 | quote = The pharmacological action of peyotline in human subjects is one of calming or sedation, rather than that of a hallucinogen. Jolly (14) has reported the production of an uneventful sleep in patients with a dosage of SO mg. At levels of as much as 240 mg (total dosage) there are no indications of sensory distortions (5). There is a dizziness and a generalized tiredness that undergoes a gentle transition into sleep. This latter quantity of drug is greater than that which would be encountered in a single dosage unit of peyote. It is certainly possible that peyotline could contribute to the pharmacological picture associated with peyote as this sedative action is noted at levels that might well be encountered in the total cactus. At low levels in man (15-30 mg) there has been described a calming effect, without overt hypnosis (14).}}{{cite thesis | vauthors = Mangner TJ | degree = Ph.D. | publisher = University of Michigan | title=Potential Psychotomimetic Antagonists. N,n -diethyl-1-methyl-3-aryl-1, 2, 5, 6-tetrahydropyridine-5-carboxamides. | date=1978 | doi=10.7302/11268 | url=https://www.proquest.com/openview/f845a6810749d00f70305960adfde737/ | archive-url=https://web.archive.org/web/20250330031605/https://media.proquest.com/media/hms/ORIG/2/9yQxJ?cit%3Aauth=MANGNER%2C+THOMAS+JOSEPH&cit%3Atitle=POTENTIAL+PSYCHOTOMIMETIC+ANTAGONISTS.+N%2CN+...&cit%3Apub=ProQuest+Dissertations+and+Theses&cit%3Avol=&cit%3Aiss=&cit%3Apg=&cit%3Adate=1978&ic=true&cit%3Aprod=ProQuest+Dissertations+%26+Theses+Global&_a=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&_s=QP3F3liRMGFAbHtX3wDWE8eO1gs%3D | archive-date=30 March 2025 | quote=In addition to compounds strictly related to mescaline just described, L. williamsii also contains at least 23 variously substituted tetrahydroisoquinolines,95 of which four have been clinically tested. The two phenolic tetrahydroisoquinolines peyotline (63a) and anhalonidine (63b) were found to produce no sensory distortions, characteristic of the effects of mescaline, at doses of up to 250 mg.98 These compounds appear to induce a calming or sedative effect rather than a psychotomimetic one. Two methylenedioxy tetrahydroisoquinolines, lophophorine (64a) and anhalonine (64b), were also found to lack any psychotomimetic-type effects.98}} However, it has been reported to have a calming or sedative effect instead.

Pellotine has been identified as a selective and potent serotonin 5-HT₆ receptor weak partial agonist, serotonin 5-HT₇ receptor inverse agonist, and serotonin 5-HT_1D receptor ligand.{{cite journal | vauthors = Poulie CB, Chan CB, Parka A, Lettorp M, Vos J, Raaschou A, Pottie E, Bundgaard MS, Sørensen LM, Cecchi CR, Märcher-Rørsted E, Bach A, Herth MM, Decker A, Jensen AA, Elfving B, Kretschmann AC, Stove CP, Kohlmeier KA, Cornett C, Janfelt C, Kornum BR, Kristensen JL | title = In Vitro and In Vivo Evaluation of Pellotine: A Hypnotic Lophophora Alkaloid | journal = ACS Pharmacol Transl Sci | volume = 6 | issue = 10 | pages = 1492–1507 | date = October 2023 | pmid = 37854625 | pmc = 10580395 | doi = 10.1021/acsptsci.3c00142 | url = }}{{cite journal | vauthors = Chan CB, Pottie E, Simon IA, Rossebø AG, Herth MM, Harpsøe K, Kristensen JL, Stove CP, Poulie CB | title = Synthesis, Pharmacological Characterization, and Binding Mode Analysis of 8-Hydroxy-Tetrahydroisoquinolines as 5-HT7 Receptor Inverse Agonists | journal = ACS Chem Neurosci | volume = 16 | issue = 3 | pages = 439–451 | date = February 2025 | pmid = 39836645 | doi = 10.1021/acschemneuro.4c00667 | url = }} In rodents, pellotine dose-dependently produces hypolocomotion, inhibits REM sleep, and promotes sleep fragmentation. The hypnotic effects of pellotine may be mediated by interactions with serotonin receptors.

Side effects of pellotine include dizziness, nausea, vertigo, and vomiting.

Ancient use

Native inhabitants of north-eastern Mexico around 810–1070 CE (according to carbon dating) are thought to have used a number of "mescal buttons" (peyote plant material) containing mescaline, pellotine, and other related alkaloids. While it is known that the cytisine-containing "mescal beans" were at least ornamental, it is unclear whether "mescal buttons" were ornamental or used for their psychoactive effects.{{Cite journal|last1=El-Seedi|first1=Hesham R.|last2=Smet|first2=Peter A. G. M. De|last3=Beck|first3=Olof|last4=Possnert|first4=Göran|last5=Bruhn|first5=Jan G.|date=2005-10-03|title=Prehistoric peyote use: Alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas|journal=Journal of Ethnopharmacology|volume=101|issue=1|pages=238–242|doi=10.1016/j.jep.2005.04.022|pmid=15990261|issn=0378-8741}}