Perrottetinene: Difference between revisions

{{Short description|Chemical compound}}

{{Infobox drug

| verifiedrevid = 355283121

| IUPAC_name = (6aS,10aR)- 6,6,9-trimethyl- 3-(2-phenylethyl)- 6a,7,8,10a-tetrahydrobenzo[c]chromen- 1-ol

| image = Perrottetinene.svg

| width = 200

<!--Clinical data-->

| tradename =

| legal_CA = Schedule II

| legal_BR = List F2

| routes_of_administration =

<!--Pharmacokinetic data-->

| metabolism =

| elimination_half-life =

| excretion =

<!--Identifiers-->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 160041-34-9

| ATC_prefix = none

| PubChem = 24766094

| ChemSpiderID = 28284856

<!--Chemical data-->

| smiles = CC1=C[C@H]2c3c(cc(cc3OC([C@H]2CC1)(C)C)CCc4ccccc4)O

| StdInChI = 1S/C24H28O2/c1-16-9-12-20-19(13-16)23-21(25)14-18(15-22(23)26-24(20,2)3)11-10-17-7-5-4-6-8-17/h4-8,13-15,19-20,25H,9-12H2,1-3H3/t19-,20+/m1/s1

| StdInChIKey = DYHMKBLKWFFFSZ-UXHICEINSA-N

'''Perrottetinene''' is a naturally occurring [[cannabinoid]] compound found in [[Marchantiophyta|liverworts]] from the genus ''[[Radula (plant)|Radula]]'' native to Japan, New Zealand and Costa Rica, namely ''[[Radula perrottetii]]'', ''[[Radula marginata]]'' and ''Radula laxiramea'',<ref>{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | display-authors = 6 | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 147–150 | date = 1999-04-01 | pmid = 32166015 | doi = 10.1515/znc-1999-3-401 | pmc = 7052475 | name-list-style = vanc | doi-access = free }}</ref><ref name="pmid30877436">{{cite journal | vauthors = Kumar A, Premoli M, Aria F, Bonini SA, Maccarinelli G, Gianoncelli A, Memo M, Mastinu A | display-authors = 6 | title = Cannabimimetic plants: are they new cannabinoidergic modulators? | journal = Planta | volume = 249 | issue = 6 | pages = 1681–1694 | date = June 2019 | pmid = 30877436 | doi = 10.1007/s00425-019-03138-x | s2cid = 253886986 }}</ref> along with a number of similar compounds.<ref>{{cite journal | vauthors = Toyota M, Kinugawa T, Asakawa Y |doi=10.1016/S0031-9422(00)90371-6|title=Bibenzyl cannabinoid and bisbibenzyl derivative from the liverwort Radula perrottetii |journal=Phytochemistry |volume=37 |issue=3 |pages=859–862 |year=1994 }}</ref><ref>{{cite journal | vauthors = Toyota M, Shimamura T, Ishii H, Renner M, [[John E. Braggins|Braggins J]], Asakawa Y | title = New bibenzyl cannabinoid from the New Zealand liverwort Radula marginata | journal = Chemical & Pharmaceutical Bulletin | volume = 50 | issue = 10 | pages = 1390–1392 | date = October 2002 | pmid = 12372871 | doi = 10.1248/cpb.50.1390 | doi-access = free }}</ref> Its chemical structure closely resembles that of [[tetrahydrocannabinol|THC]], the main active component of [[marijuana]] but with a ''cis'' rather than ''trans'' conformation and a bibenzyl tailchain instead of pentyl.<ref name="pmid33201672">{{cite journal | vauthors = Reis MH, Antunes D, Santos LH, Guimarães AC, Caffarena ER | title = Shared Binding Mode of Perrottetinene and Tetrahydrocannabinol Diastereomers inside the CB1 Receptor May Incentivize Novel Medicinal Drug Design: Findings from an ''in Silico'' Assay | journal = ACS Chemical Neuroscience | volume = 11 | issue = 24 | pages = 4289–4300 | date = December 2020 | pmid = 33201672 | doi = 10.1021/acschemneuro.0c00547 | s2cid = 227038959 }}</ref> The absolute configuration of perrottetinene was established in 2008 by an enantioselective total synthesis.<ref>{{cite journal | vauthors = Song Y, Hwang S, Gong P, Kim D, Kim S | title = Stereoselective total synthesis of (-)-perrottetinene and assignment of its absolute configuration | journal = Organic Letters | volume = 10 | issue = 2 | pages = 269–271 | date = January 2008 | pmid = 18085788 | doi = 10.1021/ol702692q }}</ref>

== Pharmacology ==

In 2018, a study showed that perrottetinene is mild to moderately [[Psychoactive drug|psychoactive]] through activation of the [[Cannabinoid receptor type 1|cannabinoid receptor 1]]. (-)-cis-PET was found to have a binding affinity of 481nM at CB1 and 225nM at CB2 while the unnatural (-)-trans-PET was found to have a binding affinity of 127nM at CB1 and 126nM at CB2, both acting as partial agonists. In terms of binding affinity this study found cis-PET to be over 22x weaker than Delta-9-THC. The same study also reported significantly reduced [[prostaglandin D2]] and [[Prostaglandin E2|E2]] brain concentrations in mice after perrottetinene administration.<ref>{{cite journal | vauthors = Chicca A, Schafroth MA, Reynoso-Moreno I, Erni R, Petrucci V, Carreira EM, Gertsch J | title = Uncovering the psychoactivity of a cannabinoid from liverworts associated with HAVOK | journal = Science Advances | volume = 4 | issue = 10 | pages = eaat2166 | date = October 2018 | pmid = 30397641 | pmc = 6200358 | doi = 10.1126/sciadv.aat2166 | bibcode = 2018SciA....4.2166C }}</ref>

Perrottetinene is structurally related to [[machaeriol A]] and other machaeriols found in ''[[Machaerium (plant)|Machaerium]]'' species.<ref>{{cite web | url=https://pubchem.ncbi.nlm.nih.gov/compound/Machaeriol-A | title=Machaeriol A }}</ref>

== See also ==

* [[Cis-THC]]

* [[CP 42,096]]

* [[KM-233]]

* [[AM-411]]

{{Reflist}}

{{Cannabinoids}}

{{Cannabinoid-stub}}