parahexyl

{{Short description|Synthetic homologue of THC}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| verifiedrevid = 447736981

| class = Cannabinoid

| IUPAC_name = 3-n-hexyl- 7,8,9,10-tetrahydro- 6,6,9-trimethyl- 6H-dibenzo(b,d)pyran- 1-ol

| image = Parahexyl-skeletal.svg

| tradename =

| legal_AU =

| legal_BR = F2

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-07-24 |title=RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 804 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |url-status=live |archive-url=https://web.archive.org/web/20230827163149/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-804-de-24-de-julho-de-2023-498447451 |archive-date=2023-08-27 |access-date=2023-08-27 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-07-25}}

| legal_CA = Schedule II

| legal_UK = Class B

| legal_US = Schedule I

| legal_DE = Anlage I

| legal_UN = P I

| routes_of_administration =

| metabolism =

| elimination_half-life =

| excretion =

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

| CAS_number = 117-51-1

| ATC_prefix = none

| PubChem = 8334

| KEGG = C22779

| synonyms = Synhexyl, n-hexyl-Δ3-THC, (C6)-Δ6a(10a)-THC

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 8031

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

| UNII = 450N174F9W

| C = 22

| H = 32

| O = 2

| smiles = Oc2cc(cc1OC(C\3=C(/c12)CC(CC/3)C)(C)C)CCCCCC

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C22H32O2/c1-5-6-7-8-9-16-13-19(23)21-17-12-15(2)10-11-18(17)22(3,4)24-20(21)14-16/h13-15,23H,5-12H2,1-4H3

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = OORFXDSWECAQLI-UHFFFAOYSA-N

}}

Parahexyl, also known as synhexyl, is a synthetic homologue of tetrahydrocannabinol (THC) which was invented in 1941 during attempts to elucidate the structure of Δ9-THC, one of the active components of cannabis.{{cite journal | vauthors = Adams R, Loewe S, Jelinek C, Wolff H | title = Tetrahydrocannabinol Homologs with Marihuana Activity. IX1. | journal = Journal of the American Chemical Society | date = July 1941 | volume = 63 | issue = 7 | pages = 1971–1973| doi = 10.1021/ja01852a052 }}{{cite journal

|vauthors=Adams R, Harfenist M, Loewe S |title=New Analogs of Tetrahydrocannabinol. XIX |journal=Journal of the American Chemical Society |volume=71 |issue=5

|pages=1624–1628 |year=1949 |doi=10.1021/ja01173a023 }}[http://www.cognitiveliberty.org/shulgin/adsarchive/parahexl.htm Ask Dr. Shulgin Online March 7, 2001]

Parahexyl is similar in both structure and activity to THC, differing only in the position of one double bond and the lengthening of the {{nowrap|3-pentyl}} chain by one CH2 group to {{nowrap|n-hexyl}}.{{cite journal | vauthors = Ono M, Shimamine M, Takahashi K, Inoue T | title = [Studies on hallucinogens. VII Synthesis of parahexyl] | language = ja | journal = Eisei Shikenjo Hokoku. Bulletin of National Institute of Hygienic Sciences | volume = 49 | issue = 92 | pages = 46–50 | year = 1974 | pmid = 4477495 }} Parahexyl produces effects typical of other cannabinoid receptor agonists in animals. It has a somewhat higher oral bioavailability than THC itself but is otherwise very similar.{{cite journal | vauthors = Fairchild MD, Jenden DJ, Mickey MR, Yale C | title = EEG effects of hallucinogens and cannabinoids using sleep-waking behavior as baseline | journal = Pharmacology, Biochemistry, and Behavior | volume = 12 | issue = 1 | pages = 99–105 | date = January 1980 | pmid = 6102770 | doi = 10.1016/0091-3057(80)90422-0 | s2cid = 24865915 }} Presumably, it acts as a CB1 receptor agonist in the same way as THC, but as there has been no research published using parahexyl since the discovery of the CB1 receptor, this has not been definitively confirmed.

Parahexyl was occasionally used as an anxiolytic in the mid-20th century, the dosage ranging from 5 mg to 90 mg.{{cite book | vauthors = Supniewski J |date=1950 |title=Farmakologia |location=Warsaw |publisher=PZWL |page=89}}{{cite web | url=https://imgur.com/a/cEsFXig | title=Synhexyl page - Supniewski J (1950). Farmakologia. Warsaw: PZWL. P. 89. }}

Parahexyl was made illegal under UN convention in 1971 on the basis of its structural similarity and similar effects profile to THC. Parahexyl was placed into the most restrictive Schedule IReport of the Technical Committee on Schedules I, II, III and I at the United Nations Conference for the adoption of a Protocol on Psychotropic Substances. 15 February 1971. E/CONF.58/L.47 as a compound with no medical use.

Isomerism

At least three isomers of parahexyl have been studied and are known to be active as cannabinoids. Parahexyl itself (i.e. the Δ6a(10a) isomer) has not had any significant use in scientific research since it was banned internationally in the early 1980s; however, the Δ8 and Δ9 isomers are both known to be cannabinoid receptor agonists, and Δ8-parahexyl has the code number JWH-124,{{cite journal | vauthors = Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, Saha B, Razdan RK | title = Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 290 | issue = 3 | pages = 1065–79 | date = September 1999 | pmid = 10454479 }}{{cite journal | vauthors = Bow EW, Rimoldi JM | title = The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation | journal = Perspectives in Medicinal Chemistry | volume = 8 | pages = 17–39 | date = 2016 | pmid = 27398024 | pmc = 4927043 | doi = 10.4137/PMC.S32171 }} while Δ9-parahexyl has been isolated from Cannabis plant material and assigned the name tetrahydrocannabihexol (THCH).{{cite journal | vauthors = Linciano P, Citti C, Russo F, Tolomeo F, Laganà A, Capriotti AL, Luongo L, Iannotta M, Belardo C, Maione S, Forni F, Vandelli MA, Gigli G, Cannazza G | title = Identification of a new cannabidiol n-hexyl homolog in a medicinal cannabis variety with an antinociceptive activity in mice: cannabidihexol | journal = Scientific Reports | volume = 10 | issue = 1 | pages = 22019 | date = December 2020 | pmid = 33328530 | pmc = 7744557 | doi = 10.1038/s41598-020-79042-2 | bibcode = 2020NatSR..1022019L }}

File:Dibenzopyran and monoterpenoid numbering of tetrahydrocannabinol.svg

class="wikitable" style="clear:left"
colspan="8" | 7 double bond isomers of parahexyl and their 30 stereoisomers
colspan="3" | Dibenzopyran numberingcolspan="2" | Monoterpenoid numberingrowspan="2" | Number of stereoisomersrowspan="2" | Natural occurrencerowspan="2" | Convention on Psychotropic Substances Schedule
Short nameChiral centersFull nameShort nameChiral centers
Δ6a(7)-parahexyl9 and 10a3-hexyl-8,9,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-olΔ4-parahexyl1 and 34Nounscheduled
Δ7-parahexyl6a, 9 and 10a3-hexyl-6a,9,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-olΔ5-parahexyl1, 3 and 48Nounscheduled
Δ8-parahexyl6a and 10a3-hexyl-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-olΔ6-parahexyl3 and 44Nounscheduled
Δ9,11-parahexyl6a and 10a3-hexyl-6a,7,8,9,10,10a-hexahydro-6,6-dimethyl-9-methylene-6H-dibenzo[b,d]pyran-1-olΔ1(7)-parahexyl3 and 44Nounscheduled
Δ9-parahexyl6a and 10a3-hexyl-6a,7,8,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-olΔ1-parahexyl3 and 44Nounscheduled
Δ10-parahexyl6a and 93-hexyl-6a,7,8,9-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-olΔ2-parahexyl1 and 44Nounscheduled
Δ6a(10a)-parahexyl93-hexyl-7,8,9,10-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-1-olΔ3-parahexyl12NoSchedule I

Note that 6H-dibenzo[b,d]pyran-1-ol is the same as 6H-benzo[c]chromen-1-ol.

{{See also|Tetrahydrocannabinol#Isomerism}}

See also

References

{{Reflist}}

{{Cannabinoids}}

{{Hallucinogens}}

{{Cannabinoidergics}}

Category:Benzochromenes

Category:Cannabinoids

Category:Hydroxyarenes