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Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice.
Pharmacol Biochem Behav. 2012 Mar; 101(1):138-47.PB

Abstract

Recently we have shown that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride (LPP1) is an antinociceptive and local anesthetic agent in rodents. Below an extended study of the pharmacological activity of LPP1 is described. In vitro LPP1 has no affinity for GABA(A), opioidergic μ and serotonergic 5-HT(1A) receptors. The total antioxidant capacity of LPP1 (1-10mM) measured as ABTS radical cation-scavenging activity showed that LPP1 has dose-dependent antioxidant properties in vitro. Low plasma concentration of this compound detected by means of HPLC method 30min after its intraperitoneal administration suggests a rapid conversion to metabolite(s) which may be responsible for its analgesic and anticonvulsant activities in vivo. In vivo the compound's influence on the electroconvulsive threshold and its activity in the maximal electroshock seizure test (MES) were evaluated. The results demonstrated that LPP1 had an anticonvulsant activity in the MES model (ED(50)=112mg/kg) and at a dose of 50mg/kg was able to elevate the electroconvulsive threshold for 8mA as compared to the vehicle-treated mice. The analgesic activity of LPP1 was investigated in the acetic acid-induced writhing test in two groups of mice: animals with sensory C-fibers ablated, and mice with C-fibers unimpaired. It proved the potent activity of this compound in both groups (approximately 85% as compared to the vehicle-treated mice). The adverse effects of LPP1 were evaluated as acute toxicity (LD(50)=747.8mg/kg) and motor coordination impairments in the rotarod and chimney tests. The results from these tests show that LPP1 at doses higher than 100mg/kg is likely to impair the motor performance of experimental animals. Concluding, LPP1 is an analgesic and anticonvulsant compound which has antioxidant properties in vitro. Further studies are necessary to assess whether the antioxidant activity and the receptor profiling demonstrated in vitro can be confirmed for its metabolite(s) that are formed in vivo.

Authors+Show Affiliations

Department of Pharmacodynamics, Jagiellonian University, Medical College, Medyczna 9, 30-688 Cracow, Poland. salat.kinga@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22227221

Citation

Salat, Kinga, et al. "Analgesic, Anticonvulsant and Antioxidant Activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one Dihydrochloride in Mice." Pharmacology, Biochemistry, and Behavior, vol. 101, no. 1, 2012, pp. 138-47.
Salat K, Moniczewski A, Salat R, et al. Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice. Pharmacol Biochem Behav. 2012;101(1):138-47.
Salat, K., Moniczewski, A., Salat, R., Janaszek, M., Filipek, B., Malawska, B., & Wieckowski, K. (2012). Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice. Pharmacology, Biochemistry, and Behavior, 101(1), 138-47. https://doi.org/10.1016/j.pbb.2011.12.014
Salat K, et al. Analgesic, Anticonvulsant and Antioxidant Activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one Dihydrochloride in Mice. Pharmacol Biochem Behav. 2012;101(1):138-47. PubMed PMID: 22227221.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analgesic, anticonvulsant and antioxidant activities of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride in mice. AU - Salat,Kinga, AU - Moniczewski,Andrzej, AU - Salat,Robert, AU - Janaszek,Monika, AU - Filipek,Barbara, AU - Malawska,Barbara, AU - Wieckowski,Krzysztof, Y1 - 2011/12/28/ PY - 2011/08/22/received PY - 2011/12/18/revised PY - 2011/12/19/accepted PY - 2012/1/10/entrez PY - 2012/1/10/pubmed PY - 2012/5/26/medline SP - 138 EP - 47 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 101 IS - 1 N2 - Recently we have shown that 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one dihydrochloride (LPP1) is an antinociceptive and local anesthetic agent in rodents. Below an extended study of the pharmacological activity of LPP1 is described. In vitro LPP1 has no affinity for GABA(A), opioidergic μ and serotonergic 5-HT(1A) receptors. The total antioxidant capacity of LPP1 (1-10mM) measured as ABTS radical cation-scavenging activity showed that LPP1 has dose-dependent antioxidant properties in vitro. Low plasma concentration of this compound detected by means of HPLC method 30min after its intraperitoneal administration suggests a rapid conversion to metabolite(s) which may be responsible for its analgesic and anticonvulsant activities in vivo. In vivo the compound's influence on the electroconvulsive threshold and its activity in the maximal electroshock seizure test (MES) were evaluated. The results demonstrated that LPP1 had an anticonvulsant activity in the MES model (ED(50)=112mg/kg) and at a dose of 50mg/kg was able to elevate the electroconvulsive threshold for 8mA as compared to the vehicle-treated mice. The analgesic activity of LPP1 was investigated in the acetic acid-induced writhing test in two groups of mice: animals with sensory C-fibers ablated, and mice with C-fibers unimpaired. It proved the potent activity of this compound in both groups (approximately 85% as compared to the vehicle-treated mice). The adverse effects of LPP1 were evaluated as acute toxicity (LD(50)=747.8mg/kg) and motor coordination impairments in the rotarod and chimney tests. The results from these tests show that LPP1 at doses higher than 100mg/kg is likely to impair the motor performance of experimental animals. Concluding, LPP1 is an analgesic and anticonvulsant compound which has antioxidant properties in vitro. Further studies are necessary to assess whether the antioxidant activity and the receptor profiling demonstrated in vitro can be confirmed for its metabolite(s) that are formed in vivo. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/22227221/Analgesic_anticonvulsant_and_antioxidant_activities_of_3_[4__3_trifluoromethyl_phenyl__piperazin_1_yl]_dihydrofuran_2_one_dihydrochloride_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(11)00435-7 DB - PRIME DP - Unbound Medicine ER -