9-Oxaergoline

9-Oxaergoline
Clinical data
Other names	(6aR,10aR)-4,6a,7,8,9,10a-hexahydro-6H-indolo[3,4-gh][1,4]benzoxazine
Drug class	Dopamine receptor agonist
ATC code	None;
Identifiers
	IUPAC name (2R,7R)-3-oxa-6,11-diazatetracyclo[7.6.1.02,7.012,16]hexadeca-1(16),9,12,14-tetraene;
PubChem CID	22813385;
ChemSpider	18531393;
ChEMBL	ChEMBL121653;
Chemical and physical data
Formula	C13H14N2O
Molar mass	214.268 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CO[C@H]2[C@H](N1)CC3=CNC4=CC=CC2=C34;
	InChI InChI=1S/C13H14N2O/c1-2-9-12-8(7-15-10(12)3-1)6-11-13(9)16-5-4-14-11/h1-3,7,11,13-15H,4-6H2/t11-,13-/m1/s1; Key:VHGCBDMLWAGBAP-DGCLKSJQSA-N;

9-Oxaergoline is a low-potency dopamine receptor agonist related to the ergolines.^[1]^[2]^[3] It is the analogue and bioisostere of ergoline in which the carbon atom at the 9 position of the ergoline ring system has been replaced with an oxygen atom.^[1]^[2]^[3] A few notable derivatives of 9-oxaergoline have been studied and characterized, including RU-29717 (N-propyl-9-oxaergoline), 6-ethyl-9-oxaergoline (EOE), and voxergolide (RU-41656), which are all substantially more potent as dopamine receptor agonists than 9-oxaergoline itself.^[3]^[4] Other derivatives, such as N-methyl-9-oxaergoline, have been characterized as well.^[3] In addition to its dopaminergic activity, RU-29717 is notable in also having affinity for serotonin receptors and in producing a short-lasting head-twitch response in rodents.^[5]^[6] The head-twitch response is notable in being a behavioral proxy of psychedelic effects caused by serotonin 5-HT_2A receptor agonism.^[7]^[8] The potential serotonergic activities of 9-oxaergoline and N-methyl-9-oxaergoline do not appear to have been reported.^[1]^[2]^[3]^[5]^[6]

References

1 2 3 Anderson PS, Baldwin JJ, McClure DE, Lundell GF, Jones JH (1982). "A new class of D-heteroergolines: total synthesis and resolution of a 9-oxaergoline, 4,6,6a,8,9,10a-hexahydro-7-ethyl-7H-indolo[3,4-gh][1,4]benzoxazine". The Journal of Organic Chemistry. 47 (11): 2184–2187. doi:10.1021/jo00132a040. ISSN 0022-3263.
1 2 3 Anderson PS, Baldwin JJ, McClure DE, Lundell GF, Jones JH, Randall WC, et al. (March 1983). "Synthesis of (7R)-7H-indolo[3,4-gh][1,4]benzoxazines, a new class of D-heteroergolines with dopamine agonist activity". Journal of Medicinal Chemistry. 26 (3): 363–367. doi:10.1021/jm00357a010. PMID 6298427.
1 2 3 4 5 Nedelec L, Pierdet A, Fauveau P, Euvrard C, Proulx-Ferland L, Dumont C, et al. (April 1983). "Synthesis and central dopaminergic activities of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-9-oxaergolines]". Journal of Medicinal Chemistry. 26 (4): 522–527. doi:10.1021/jm00358a012. PMID 6834383.
↑ Willig F, Van de Velde D, Laurent J, M'Harzi M, Delacour J (1992). "The Roman strains of rats as a psychogenetic tool for pharmacological investigation of working memory: example with RU 41656". Psychopharmacology. 107 (2–3): 415–424. doi:10.1007/BF02245169. PMID 1352059.
1 2 Boissier JR, Euvrard C, Oberlander C, Laurent J, Dumont C, Labrie F (February 1983). "Comparative study of central dopaminergic properties of RU 29717 (N-propyl-9-oxaergoline) and pergolide". European Journal of Pharmacology. 87 (2–3): 183–189. doi:10.1016/0014-2999(83)90328-x. PMID 6857756. The relatively low affinity of pergolide for 5-HT receptors compared to that of RU 29717 is in keeping with the lack of biochemical evidence of altered 5-HT function (Fuller et al., 1979). It has been observed that RU 29717 induced short-lasting head-twitches in mice (results not shown). This result, favouring a 5-HT agonist property could be of value for its potential therapeutic interest (Silbergeld and Hruska, 1979).
1 2 Hazelhoff B, De Vries JB, Dijkstra D, Mulder TB, Timmermans PB, Wynberg H, et al. (May 1986). "Neuropharmacological profile of a new series of dopamine agonists: N-n-propyl-hexahydronaphthoxazines". European Journal of Pharmacology. 124 (1–2): 93–106. doi:10.1016/0014-2999(86)90128-7. PMID 3720849.
↑ Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. PMC 5787039. PMID 28224459.
↑ Alexander L, Anderson D, Baxter L, Claydon M, Rucker J, Robinson ES (October 2024). "Preclinical models for evaluating psychedelics in the treatment of major depressive disorder". British Journal of Pharmacology bph.17370. doi:10.1111/bph.17370. PMID 39467003.

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[AndersonBaldwinMcClure1982-1] 1 2 3 Anderson PS, Baldwin JJ, McClure DE, Lundell GF, Jones JH (1982). "A new class of D-heteroergolines: total synthesis and resolution of a 9-oxaergoline, 4,6,6a,8,9,10a-hexahydro-7-ethyl-7H-indolo[3,4-gh][1,4]benzoxazine". The Journal of Organic Chemistry. 47 (11): 2184–2187. doi:10.1021/jo00132a040. ISSN 0022-3263.

[AndersonBaldwinMcClure1983-2] 1 2 3 Anderson PS, Baldwin JJ, McClure DE, Lundell GF, Jones JH, Randall WC, et al. (March 1983). "Synthesis of (7R)-7H-indolo[3,4-gh][1,4]benzoxazines, a new class of D-heteroergolines with dopamine agonist activity". Journal of Medicinal Chemistry. 26 (3): 363–367. doi:10.1021/jm00357a010. PMID 6298427.

[NedelecPierdetFauveau1983-3] 1 2 3 4 5 Nedelec L, Pierdet A, Fauveau P, Euvrard C, Proulx-Ferland L, Dumont C, et al. (April 1983). "Synthesis and central dopaminergic activities of (+/-)-hexahydro-7H-indolo[3,4-gh][1,4]benzoxazine derivatives [(+/-)-9-oxaergolines]". Journal of Medicinal Chemistry. 26 (4): 522–527. doi:10.1021/jm00358a012. PMID 6834383.

[WilligVandeVeldeLaurent1992-4] Willig F, Van de Velde D, Laurent J, M'Harzi M, Delacour J (1992). "The Roman strains of rats as a psychogenetic tool for pharmacological investigation of working memory: example with RU 41656". Psychopharmacology. 107 (2–3): 415–424. doi:10.1007/BF02245169. PMID 1352059.

[BoissierEuvrardOberlander1983-5] 1 2 Boissier JR, Euvrard C, Oberlander C, Laurent J, Dumont C, Labrie F (February 1983). "Comparative study of central dopaminergic properties of RU 29717 (N-propyl-9-oxaergoline) and pergolide". European Journal of Pharmacology. 87 (2–3): 183–189. doi:10.1016/0014-2999(83)90328-x. PMID 6857756. The relatively low affinity of pergolide for 5-HT receptors compared to that of RU 29717 is in keeping with the lack of biochemical evidence of altered 5-HT function (Fuller et al., 1979). It has been observed that RU 29717 induced short-lasting head-twitches in mice (results not shown). This result, favouring a 5-HT agonist property could be of value for its potential therapeutic interest (Silbergeld and Hruska, 1979).

[HazelhoffDeVriesDijkstraMulder1986-6] 1 2 Hazelhoff B, De Vries JB, Dijkstra D, Mulder TB, Timmermans PB, Wynberg H, et al. (May 1986). "Neuropharmacological profile of a new series of dopamine agonists: N-n-propyl-hexahydronaphthoxazines". European Journal of Pharmacology. 124 (1–2): 93–106. doi:10.1016/0014-2999(86)90128-7. PMID 3720849.

[HalberstadtGeyer2018-7] Halberstadt AL, Geyer MA (2018). "Effect of Hallucinogens on Unconditioned Behavior". Behavioral Neurobiology of Psychedelic Drugs. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 159–199. doi:10.1007/7854_2016_466. ISBN 978-3-662-55878-2. PMC 5787039. PMID 28224459.

[AlexanderAndersonBaxter2024-8] Alexander L, Anderson D, Baxter L, Claydon M, Rucker J, Robinson ES (October 2024). "Preclinical models for evaluating psychedelics in the treatment of major depressive disorder". British Journal of Pharmacology bph.17370. doi:10.1111/bph.17370. PMID 39467003.

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9-Oxaergoline

See also

References