Thiofentanil

Structural formula
General
Surname	Thiofentanil
other names	R 31826; 4- ( N -propanoylanilino) -1- (2-thiophen-2-ylethyl) piperidine-4-carboxylic acid methyl ester;
Molecular formula	C 22 H 28 N 2 O 3 S
External identifiers / databases
PubChem	173761
Wikidata	Q26882856
properties
Molar mass	400.53 g mol −1
Physical state	firmly
safety instructions
GHS hazard labeling ; no classification available
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Thiofentanil is the 2-thienyl analogue of carfentanil . It was first described in the literature in 1976. Thiofentanil is a highly potent opioid with a slightly lower analgesic potency than carfentanil. The following values were determined in the rat (iv, tail withdrawal): 7159-8676 times the morphine potency for thiofentanil and 7682-10031 times the morphine potency for carfentanil (in direct comparison). In contrast to carfentanil, thiofentanil initially met with little interest, but was studied in more detail in China in the early 1990s, where it was compared with etorphine . In addition, the physical addiction potential with chronic administration was examined.

properties

Thiofentanil shows similar pharmacological properties as etorphine . The analgesic potency in the mouse (ip, hot plate) is 3260 times that of morphine , 22 times that of fentanyl and 1.5 times that of etorphine. The immobilizing potency is 2-3 times higher than that of etorphine. Studies on mice, rats and monkeys showed that thiofentanil has a significantly lower physical addiction potential than morphine at analgesically equivalent doses . No physical dependence was observed in rats when thiofentanil was administered intravenously every hour over a period of 72 hours (72 times iv over 3 days). In monkeys after chronic administration for 5 months (20 weeks) there were also no signs of physical dependence.

According to these results, thiofentanil, like dihydroetorphine , could be important for human pain management and detoxification of opioid addicts. In order to be able to better assess the addictive potential of thiofentanil, further studies are required, in particular the direct comparison with the isomeric 3-thienyl analogue, carfentanil, sufentanil , and dihydroetorphine. Studies with dihydroetorphine and ohmefentanyl showed that the physical addiction potential of opioids does not have to correlate with analgesic potency and effectiveness.

Intensity of the abstinence syndrome after chronic administration of thiofentanil compared to morphine and saline:

substance	Intensity withdrawal syndrome
Morphine	25.33
Thiofentanil	7.60
Saltworks	5.60

Others

Thiofentanil (R 31826) should not be confused with thiafentanil and thiofentanyl . Thiafentanil is the analogous methoxyacetamide (methyl {1- [2- (2-thienyl) ethyl] -4- ( N -phenyl-methoxyacetamido) piperidine-4-carboxylate}), while thiofentanyl is the corresponding fentanyl derivative ( N -phenyl- N - {1- [2- (2-thienyl) ethyl] piperidin-4-yl} propanamide).

The 3-thienyl analogue isomeric to thiofentanil (methyl {1- [2- (3-thienyl) ethyl] -4- ( N -phenylpropanamido) piperidine-4-carboxylate}) is about 1.5 times more potent than thiofentanil and about 1.3 times more potent than carfentanil. In mice (iv hot plate) it was 16,600 times more potent than morphine, carfentanil for comparison achieved 10,500 times the morphine potency.

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ PG Van Daele, MF De Bruyn, JM Boey, S. Sanczuk, JT Agten, PA Janssen: Synthetic analgesics: N- (1- [2-arylethyl] -4-substituted 4-piperidinyl) N-arylalkanamides . In: drug research . tape 26 , no. 8 , 1976, p. 1521-1531 , PMID 12769 .
^ WF Van Bever, CJ Niemegeers, KH Schellekens, PA Janssen: N-4-Substituted 1- (2-arylethyl) -4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin . In: drug research . tape 26 , no. 8 , 1976, p. 1548-1551 , PMID 12771 .
↑ ^a ^b ^c ^d ^e M. Li, JW Zheng, YH Liu, JL Zhang, LN Liu, ZJ Cai: [Experimental study on the principal effects and dependence potential of thiofentanil] . In: Yao Xue Xue Bao = Acta Pharmaceutica Sinica . tape 26 , no. 4 , 1991, ISSN 0513-4870 , pp. 241-245 , PMID 1683505 .
↑ M. Huang, DX Wang, BY Qin: Dihydroetorphine, a Potent Opioid with low Dependence Potential . In: Regulatory Peptides . tape 53 , 1994, pp. 81-82 .
↑ BY Qin, M. Huang, YC Zhang, H. Miao: Comparison of the Dependence Potential of Dihydroetorphine, Etorphine and Morphine . In: Regulatory Peptides . tape 54 , 1994, pp. 237-238 .
↑ BY Qin, DX Wang, M. Huang: The Application of Dihydroetorphine to Detoxification of Heroin Addicts . In: Regulatory Peptides . tape 53 , 1994, pp. 293-294 .
↑ Bo-Yi Qin: Advances in Dihydroetorphine: From Analgesia to Detoxification . In: Drug Development Research . tape 39 , 1994, pp. 131-134 .
↑ Guo, GW; He, Y .; Jin, WQ; Zou, Y .; Zhu, YC; Chi, ZQ (2000). Comparison of physical dependence of ohmefentanyl stereoisomers in mice . In: Life Sciences 67 (2): 113-120.
↑ Jerome R. Bagley, Sheela A. Thomas, Frieda G. Rudo, H. Kenneth Spencer, Brian M. Doorley, Michael H. Ossipov, Thomas P. Jerussi, Mark J. Benvenga, Theodore Spaulding: New 1- (heterocyclylalkyl) -4- (propionanilido) -4-piperidinyl methyl ester and methylene methyl ether analgesics . In: Journal of Medicinal Chemistry . tape 34 , no. 2 , 2002, p. 827-841 , doi : 10.1021 / jm00106a051 .

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[2] PG Van Daele, MF De Bruyn, JM Boey, S. Sanczuk, JT Agten, PA Janssen: Synthetic analgesics: N- (1- [2-arylethyl] -4-substituted 4-piperidinyl) N-arylalkanamides . In: drug research . tape 26 , no. 8 , 1976, p. 1521-1531 , PMID 12769 .

[van_Bever-3] WF Van Bever, CJ Niemegeers, KH Schellekens, PA Janssen: N-4-Substituted 1- (2-arylethyl) -4-piperidinyl-N-phenylpropanamides, a novel series of extremely potent analgesics with unusually high safety margin . In: drug research . tape 26 , no. 8 , 1976, p. 1548-1551 , PMID 12771 .

[Li-4] M. Li, JW Zheng, YH Liu, JL Zhang, LN Liu, ZJ Cai: [Experimental study on the principal effects and dependence potential of thiofentanil] . In: Yao Xue Xue Bao = Acta Pharmaceutica Sinica . tape 26 , no. 4 , 1991, ISSN 0513-4870 , pp. 241-245 , PMID 1683505 .

[Huang-5] M. Huang, DX Wang, BY Qin: Dihydroetorphine, a Potent Opioid with low Dependence Potential . In: Regulatory Peptides . tape 53 , 1994, pp. 81-82 .

[Zhang-6] BY Qin, M. Huang, YC Zhang, H. Miao: Comparison of the Dependence Potential of Dihydroetorphine, Etorphine and Morphine . In: Regulatory Peptides . tape 54 , 1994, pp. 237-238 .

[Qin,_B.Y.-7] BY Qin, DX Wang, M. Huang: The Application of Dihydroetorphine to Detoxification of Heroin Addicts . In: Regulatory Peptides . tape 53 , 1994, pp. 293-294 .

[Qin-8] Bo-Yi Qin: Advances in Dihydroetorphine: From Analgesia to Detoxification . In: Drug Development Research . tape 39 , 1994, pp. 131-134 .

[9] Guo, GW; He, Y .; Jin, WQ; Zou, Y .; Zhu, YC; Chi, ZQ (2000). Comparison of physical dependence of ohmefentanyl stereoisomers in mice . In: Life Sciences 67 (2): 113-120.

[10] Jerome R. Bagley, Sheela A. Thomas, Frieda G. Rudo, H. Kenneth Spencer, Brian M. Doorley, Michael H. Ossipov, Thomas P. Jerussi, Mark J. Benvenga, Theodore Spaulding: New 1- (heterocyclylalkyl) -4- (propionanilido) -4-piperidinyl methyl ester and methylene methyl ether analgesics . In: Journal of Medicinal Chemistry . tape 34 , no. 2 , 2002, p. 827-841 , doi : 10.1021 / jm00106a051 .