Tiflucarbine

Tiflucarbine
Clinical data
Other names	BAY-P 4495; TVX P 4495
Drug class	Serotonin receptor agonist
ATC code	None;
Identifiers
	IUPAC name 9-Ethyl-4-fluoro-1-methyl-7,8,9,10-tetrahydro-6H-pyrido[4,3-b]thieno[3,2-e]indole;
CAS Number	89875-86-5;
PubChem CID	65677;
ChemSpider	59106;
UNII	M2108NUY0C;
ChEMBL	ChEMBL2104715;
CompTox Dashboard (EPA)	DTXSID90237924 ;
Chemical and physical data
Formula	C16H17FN2S
Molar mass	288.38 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCN1CCC2=C(C1)C3=C4C(=CSC4=C(C=C3N2)F)C;
	InChI InChI=1S/C16H17FN2S/c1-3-19-5-4-12-10(7-19)15-13(18-12)6-11(17)16-14(15)9(2)8-20-16/h6,8,18H,3-5,7H2,1-2H3; Key:BNKIWXODDDABSJ-UHFFFAOYSA-N;

Tiflucarbine (BAY-P 4495 or TVX P 4495) is an experimental drug which acts as an agonist of the 5-HT₁ and 5-HT₂ serotonin receptor families, and also acts as a calmodulin inhibitor. It has antidepressant effects in animal studies.^[1]^[2]^[3]^[4] It produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.^[2]^[5] In addition, it partially substituted for DOM and 8-OH-DPAT in rodent drug discrimination tests, with further generalization but concomitant substantial behavioral disruption in 5-MeO-DMT-trained rodents.^[2] Tiflucarbine is similar in structure to but distinct from β-carbolines, instead being a γ-carboline.

References

↑ Maj J, Rogóz Z, Sowińska H, Zalewski Z (1987). "Some central effects of tiflucarbine, a new potential antidepressant drug". Polish Journal of Pharmacology and Pharmacy. 39 (1): 63–74. PMID 2823240.
1 2 3 Glennon RA, De Vry J, Spencer DG, Glaser T (December 1990). "Stimulus properties of tiflucarbine: a novel antidepressant agent". Pharmacol Biochem Behav. 37 (4): 769–771. doi:10.1016/0091-3057(90)90561-u. PMID 2151199. THE structurally novel antidepressant tiflucarbine (TVX P 4495) has been demonstrated to act primarily via a serotonergic mechanism (2,3). Tiflucarbine binds both at 5-HT1 and 5-HT2 sites and displays little affinity (i.e., K i >3,000 nM) for adrenergic, dopaminergic, gaba, benzodiazepine, and other binding sites (3). In behavioral studies with rodents, tiflucarbine produces effects indicative of 5-HT1 agonism (such as forepaw treading, hindlimb abduction and flat body posture) and 5-HT2 agonism (such as head-twitch behavior) (3). Whereas its affinity for 5-HTI sites is not particularly high, tiflucarbine binds at 5-HT2 sites with an affinity (K i - 115 nM) comparable to that of the 5-HT2 agonist l-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) (3). Taken together, the available evidence suggests that this agent may be a novel 5-HT2 agonist.
↑ Schmidt BH, Glaser T, Seidel PR, Traber J (December 1990). "Evidence for a specific recognition site for tiflucarbine on calmodulin". European Journal of Pharmacology. 189 (6): 411–418. doi:10.1016/0922-4106(90)90039-z. PMID 1963605.
↑ Hegemann L, Fruchtmann R, Bonnekoh B, Schmidt BH, Traber J, Mahrle G, et al. (1991). "Effects of tiflucarbine as a dual protein kinase C/calmodulin antagonist on proliferation of human keratinocytes and release of reactive oxygen species from human leukocytes". Archives of Dermatological Research. 283 (7): 456–460. doi:10.1007/BF00371782. PMID 1801655.
↑ Glaser, T., Dompert, W. U., Horvath, E., Schuurman, T., Spencer, D. G., & Traber, J. (1987, November). Tiflucarbine, a potential new antidepressant: Biochemical and behavioral pharmacology. In Abstract P22, International Conference on the Behavioral Pharmacology of Serotonin. https://scholar.google.com/scholar?cluster=15335975313192901460

[1] Maj J, Rogóz Z, Sowińska H, Zalewski Z (1987). "Some central effects of tiflucarbine, a new potential antidepressant drug". Polish Journal of Pharmacology and Pharmacy. 39 (1): 63–74. PMID 2823240.

[GlennonDeVrySpencer1990-2] 1 2 3 Glennon RA, De Vry J, Spencer DG, Glaser T (December 1990). "Stimulus properties of tiflucarbine: a novel antidepressant agent". Pharmacol Biochem Behav. 37 (4): 769–771. doi:10.1016/0091-3057(90)90561-u. PMID 2151199. THE structurally novel antidepressant tiflucarbine (TVX P 4495) has been demonstrated to act primarily via a serotonergic mechanism (2,3). Tiflucarbine binds both at 5-HT1 and 5-HT2 sites and displays little affinity (i.e., K i >3,000 nM) for adrenergic, dopaminergic, gaba, benzodiazepine, and other binding sites (3). In behavioral studies with rodents, tiflucarbine produces effects indicative of 5-HT1 agonism (such as forepaw treading, hindlimb abduction and flat body posture) and 5-HT2 agonism (such as head-twitch behavior) (3). Whereas its affinity for 5-HTI sites is not particularly high, tiflucarbine binds at 5-HT2 sites with an affinity (K i - 115 nM) comparable to that of the 5-HT2 agonist l-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) (3). Taken together, the available evidence suggests that this agent may be a novel 5-HT2 agonist.

[3] Schmidt BH, Glaser T, Seidel PR, Traber J (December 1990). "Evidence for a specific recognition site for tiflucarbine on calmodulin". European Journal of Pharmacology. 189 (6): 411–418. doi:10.1016/0922-4106(90)90039-z. PMID 1963605.

[4] Hegemann L, Fruchtmann R, Bonnekoh B, Schmidt BH, Traber J, Mahrle G, et al. (1991). "Effects of tiflucarbine as a dual protein kinase C/calmodulin antagonist on proliferation of human keratinocytes and release of reactive oxygen species from human leukocytes". Archives of Dermatological Research. 283 (7): 456–460. doi:10.1007/BF00371782. PMID 1801655.

[GlaserDompertHorvath1987-5] Glaser, T., Dompert, W. U., Horvath, E., Schuurman, T., Spencer, D. G., & Traber, J. (1987, November). Tiflucarbine, a potential new antidepressant: Biochemical and behavioral pharmacology. In Abstract P22, International Conference on the Behavioral Pharmacology of Serotonin. https://scholar.google.com/scholar?cluster=15335975313192901460

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See also

References