Trimethylthiazoline

Trimethylthiazoline
Names
	Preferred IUPAC name 2,4,5-Trimethyl-4,5-dihydro-1,3-thiazole
	Other names Fox odor
Identifiers
CAS Number	4145-93-1 [EPA];
3D model (JSmol)	Interactive image;
ChemSpider	231591;
PubChem CID	263626;
CompTox Dashboard (EPA)	DTXSID20294803;
	InChI InChI=1S/C6H11NS/c1-4-5(2)8-6(3)7-4/h4-5H,1-3H3 Key: CIEKNJJOENYFQL-UHFFFAOYSA-N;
	SMILES CC1C(SC(=N1)C)C;
Properties
Chemical formula	C6H11NS
Molar mass	129.22 g·mol−1
Appearance	Light yellow liquid
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). (what is ?) Infobox references

Trimethylthiazoline (TMT; sometimes called fox odor) is a constituent of fox urine and feces that may be an innately aversive odor to rodents.^[1] The chemical is liquid at room temperature and has a very light yellow color which darkens on oxygen exposure over time.

Sources

TMT was first isolated from cooked beef in 1977,^[2] and has been identified also in non-animal material such as wheat flour extrudates.^[3] It was identified in fox feces by Vernet-Maury in 1980.^[4]

Effects

Vernet-Maury reported that TMT is effective at inducing antipredator behavior in rats.^[5]

TMT has been called an "innate threat stimulus" because of how it "induces a number of fear and defensive behaviors" in naive mice and rats.^[6]

Not all research has come to the same conclusions, however; with some questioning the role of TMT in the aversive effects of fox feces.^[7]^[8] One study, for example, found that cat odor, but not TMT, elicits specific defensive behaviors in rats.^[9]

Immunoprecipitation of RNA transcripts of murine olfactory cells have identified an enriched pool of odorant receptors activated by TMT, including five receptors (Olfr20, Olfr30, Olfr57, Olfr376, Olfr491) that localize to the dorsal portion of the olfactory epithelium which can mediate fear behaviour.^[10]

References

^ Rosen JB, Asok A, Chakraborty T (2015). "The smell of fear: innate threat of 2,5-dihydro-2,4,5-trimethylthiazoline, a single molecule component of a predator odor". Frontiers in Neuroscience. 9: 292. doi:10.3389/fnins.2015.00292. PMC 4548190. PMID 26379483.
^ Mussinan CJ, Wilson RA, Katz I, Hruza A, Vock MH (1976). "Identification and Flavor Properties of Some 3-Oxazolines and 3-Thiazolines Isolated from Cooked Beef". Phenolic, Sulfur, and Nitrogen Compounds in Food Flavors. ACS Symposium Series. Vol. 26. pp. 133–145. doi:10.1021/bk-1976-0026.ch009. ISBN 0-8412-0330-X.
^ Bredie WL, Mottram DS, Guy RC (February 2002). "Effect of temperature and pH on the generation of flavor volatiles in extrusion cooking of wheat flour". Journal of Agricultural and Food Chemistry. 50 (5): 1118–25. doi:10.1021/jf0111662. PMID 11853492.
^ Vernet-Maury E, Polak EH, Demael A (July 1984). "Structure-activity relationship of stress-inducing odorants in the rat". Journal of Chemical Ecology. 10 (7): 1007–18. Bibcode:1984JCEco..10.1007V. doi:10.1007/BF00987509. PMID 24318845. S2CID 21326349.
^ Fendt M, Endres T, Lowry CA, Apfelbach R, McGregor IS (2005). "TMT-induced autonomic and behavioral changes and the neural basis of its processing". Neuroscience and Biobehavioral Reviews. 29 (8): 1145–56. doi:10.1016/j.neubiorev.2005.04.018. PMID 16099043. S2CID 28347024.
^ Goswami S, Rodríguez-Sierra O, Cascardi M, Paré D (2013). "Animal models of post-traumatic stress disorder: face validity". Frontiers in Neuroscience. 7: 89. doi:10.3389/fnins.2013.00089. PMC 3668155. PMID 23754973.
^ Rampin O, Jerôme N, Saint-Albin A, Ouali C, Boué F, Meunier N, Nielsen BL (February 2018). "Where is the TMT? GC-MS analyses of fox feces and behavioral responses of rats to fear-inducing odors". Chemical Senses. 43 (2): 105–115. doi:10.1093/chemse/bjx075. PMID 29228118.
^ Blanchard DC, Markham C, Yang M, Hubbard D, Madarang E, Blanchard RJ (April 2003). "Failure to produce conditioning with low-dose trimethylthiazoline or cat feces as unconditioned stimuli". Behavioral Neuroscience. 117 (2): 360–8. doi:10.1037/0735-7044.117.2.360. PMID 12708532.
^ McGregor IS, Schrama L, Ambermoon P, Dielenberg RA (February 2002). "Not all 'predator odours' are equal: cat odour but not 2,4,5 trimethylthiazoline (TMT; fox odour) elicits specific defensive behaviours in rats". Behavioural Brain Research. 129 (1–2): 1–16. doi:10.1016/S0166-4328(01)00324-2. PMID 11809490. S2CID 25158077.
^ Jiang Y, Gong NN, Hu XS, Ni MJ, Pasi R, Matsunami H (October 2015). "Molecular profiling of activated olfactory neurons identifies odorant receptors for odors in vivo". Nature Neuroscience. 18 (10): 1446–54. doi:10.1038/nn.4104. PMC 4583814. PMID 26322927.

[1] Rosen JB, Asok A, Chakraborty T (2015). "The smell of fear: innate threat of 2,5-dihydro-2,4,5-trimethylthiazoline, a single molecule component of a predator odor". Frontiers in Neuroscience. 9: 292. doi:10.3389/fnins.2015.00292. PMC 4548190. PMID 26379483.

[2] Mussinan CJ, Wilson RA, Katz I, Hruza A, Vock MH (1976). "Identification and Flavor Properties of Some 3-Oxazolines and 3-Thiazolines Isolated from Cooked Beef". Phenolic, Sulfur, and Nitrogen Compounds in Food Flavors. ACS Symposium Series. Vol. 26. pp. 133–145. doi:10.1021/bk-1976-0026.ch009. ISBN 0-8412-0330-X.

[3] Bredie WL, Mottram DS, Guy RC (February 2002). "Effect of temperature and pH on the generation of flavor volatiles in extrusion cooking of wheat flour". Journal of Agricultural and Food Chemistry. 50 (5): 1118–25. doi:10.1021/jf0111662. PMID 11853492.

[4] Vernet-Maury E, Polak EH, Demael A (July 1984). "Structure-activity relationship of stress-inducing odorants in the rat". Journal of Chemical Ecology. 10 (7): 1007–18. Bibcode:1984JCEco..10.1007V. doi:10.1007/BF00987509. PMID 24318845. S2CID 21326349.

[5] Fendt M, Endres T, Lowry CA, Apfelbach R, McGregor IS (2005). "TMT-induced autonomic and behavioral changes and the neural basis of its processing". Neuroscience and Biobehavioral Reviews. 29 (8): 1145–56. doi:10.1016/j.neubiorev.2005.04.018. PMID 16099043. S2CID 28347024.

[6] Goswami S, Rodríguez-Sierra O, Cascardi M, Paré D (2013). "Animal models of post-traumatic stress disorder: face validity". Frontiers in Neuroscience. 7: 89. doi:10.3389/fnins.2013.00089. PMC 3668155. PMID 23754973.

[7] Rampin O, Jerôme N, Saint-Albin A, Ouali C, Boué F, Meunier N, Nielsen BL (February 2018). "Where is the TMT? GC-MS analyses of fox feces and behavioral responses of rats to fear-inducing odors". Chemical Senses. 43 (2): 105–115. doi:10.1093/chemse/bjx075. PMID 29228118.

[8] Blanchard DC, Markham C, Yang M, Hubbard D, Madarang E, Blanchard RJ (April 2003). "Failure to produce conditioning with low-dose trimethylthiazoline or cat feces as unconditioned stimuli". Behavioral Neuroscience. 117 (2): 360–8. doi:10.1037/0735-7044.117.2.360. PMID 12708532.

[9] McGregor IS, Schrama L, Ambermoon P, Dielenberg RA (February 2002). "Not all 'predator odours' are equal: cat odour but not 2,4,5 trimethylthiazoline (TMT; fox odour) elicits specific defensive behaviours in rats". Behavioural Brain Research. 129 (1–2): 1–16. doi:10.1016/S0166-4328(01)00324-2. PMID 11809490. S2CID 25158077.

[pmid26322927-10] Jiang Y, Gong NN, Hu XS, Ni MJ, Pasi R, Matsunami H (October 2015). "Molecular profiling of activated olfactory neurons identifies odorant receptors for odors in vivo". Nature Neuroscience. 18 (10): 1446–54. doi:10.1038/nn.4104. PMC 4583814. PMID 26322927.

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