Tags

Type your tag names separated by a space and hit enter

3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury.
Toxicol Mech Methods. 2015; 25(7):514-23.TM

Abstract

PURPOSE

There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed.

METHODS

Antiallodynic and antihyperalgesic activities of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor-impairing properties were evaluated in the rotarod test. Microscopic examinations of the sciatic nerve were performed using electron microscope. In immunohistochemical assays the content of NGF in the sciatic nerve after single or repeated administration of test drugs was assessed.

RESULTS

Microscopic examinations of the sciatic nerve revealed ultrastructural changes in nerve fibers indicating for neurodegenerative processes induced by CCI. Seven days after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test (ED50 values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at dose range 0.5-100 mg/kg induced motor deficits in the rotarod test. In immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF content.

CONCLUSIONS

LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain.

Authors+Show Affiliations

a Department of Pharmacodynamics , Chair of Pharmacodynamics, Medical College, Jagiellonian University , Cracow , Poland .a Department of Pharmacodynamics , Chair of Pharmacodynamics, Medical College, Jagiellonian University , Cracow , Poland .b Department of Pharmacobiology , Medical College, Jagiellonian University , Cracow , Poland .c Department of Neuroanatomy , Institute of Zoology, Jagiellonian University , Cracow , Poland .b Department of Pharmacobiology , Medical College, Jagiellonian University , Cracow , Poland .a Department of Pharmacodynamics , Chair of Pharmacodynamics, Medical College, Jagiellonian University , Cracow , Poland .d Department of Organic Chemistry , Chair of Organic Chemistry, Medical College, Jagiellonian University , Cracow , Poland , and.e Department of Physicochemical Drug Analysis , Chair of Pharmaceutical Chemistry, Medical College, Jagiellonian University , Cracow , Poland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25996035

Citation

Sałat, Kinga, et al. "3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and Pregabalin Attenuate Tactile Allodynia in the Mouse Model of Chronic Constriction Injury." Toxicology Mechanisms and Methods, vol. 25, no. 7, 2015, pp. 514-23.
Sałat K, Witalis J, Zadrożna M, et al. 3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury. Toxicol Mech Methods. 2015;25(7):514-23.
Sałat, K., Witalis, J., Zadrożna, M., Sołtys, Z., Nowak, B., Filipek, B., Więckowski, K., & Malawska, B. (2015). 3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury. Toxicology Mechanisms and Methods, 25(7), 514-23. https://doi.org/10.3109/15376516.2015.1034333
Sałat K, et al. 3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and Pregabalin Attenuate Tactile Allodynia in the Mouse Model of Chronic Constriction Injury. Toxicol Mech Methods. 2015;25(7):514-23. PubMed PMID: 25996035.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3-[4-(3-Trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one and pregabalin attenuate tactile allodynia in the mouse model of chronic constriction injury. AU - Sałat,Kinga, AU - Witalis,Jadwiga, AU - Zadrożna,Monika, AU - Sołtys,Zbigniew, AU - Nowak,Barbara, AU - Filipek,Barbara, AU - Więckowski,Krzysztof, AU - Malawska,Barbara, Y1 - 2015/05/21/ PY - 2015/5/22/entrez PY - 2015/5/23/pubmed PY - 2016/8/3/medline KW - Chronic constriction injury of the sciatic nerve KW - dihydrofuran-2-one KW - mice KW - nerve growth factor KW - pregabalin SP - 514 EP - 23 JF - Toxicology mechanisms and methods JO - Toxicol Mech Methods VL - 25 IS - 7 N2 - PURPOSE: There is a strong medical demand to search for novel, more efficacious and safer than available, analgesics for the treatment of neuropathic pain. This study investigated antinociceptive activity of intraperitoneally administered 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) and pregabalin in the chronic constriction injury (CCI) model of neuropathic pain in mice and evaluated these drugs' influence on motor coordination. In addition, microscopic examinations of the sciatic nerve were performed to assess, if a surgical method or drug treatment caused changes in the structure of this nerve. Moreover, the alterations of nerve growth factor (NGF) content after drug treatment were assessed. METHODS: Antiallodynic and antihyperalgesic activities of LPP1 and pregabalin were assessed in the von Frey and hot plate tests. Motor-impairing properties were evaluated in the rotarod test. Microscopic examinations of the sciatic nerve were performed using electron microscope. In immunohistochemical assays the content of NGF in the sciatic nerve after single or repeated administration of test drugs was assessed. RESULTS: Microscopic examinations of the sciatic nerve revealed ultrastructural changes in nerve fibers indicating for neurodegenerative processes induced by CCI. Seven days after CCI surgery LPP1 and pregabalin reduced tactile allodynia in von Frey test (ED50 values were 1.5 and 15.4 mg/kg, respectively). None of the test drugs at dose range 0.5-100 mg/kg induced motor deficits in the rotarod test. In immunohistochemical assays repeated doses of pregabalin and LPP1 elevated NGF content. CONCLUSIONS: LPP1 has antiallodynic properties and is an interesting lead structure in the search for novel analgesics used in neuropathic pain. SN - 1537-6524 UR - https://www.unboundmedicine.com/medline/citation/25996035/3_[4__3_Trifluoromethyl_phenyl__piperazin_1_yl]_dihydrofuran_2_one_and_pregabalin_attenuate_tactile_allodynia_in_the_mouse_model_of_chronic_constriction_injury_ L2 - https://www.tandfonline.com/doi/full/10.3109/15376516.2015.1034333 DB - PRIME DP - Unbound Medicine ER -