title: α-Spinasterol, a TRPV1 receptor antagonist, elevates the seizure threshold in three acute seizure tests in mice.
abstract: α-Spinasterol is a plant-derived compound which was reported to act as a selective antagonist for the transient receptor potential vanilloid 1 (TRPV1) receptor. Several studies revealed that the TRPV1 receptors might modulate seizure activity in animal models of seizures and epilepsy. The aim of the present study was to investigate the effect of α-spinasterol on the seizure threshold in three acute models of seizures, i.e., in the intravenous (i.v.) pentylenetetrazole (PTZ) seizure test, in the maximal electroshock seizure threshold (MEST) test and in the model of psychomotor seizures induced by 6 Hz stimulation in mice. Our results revealed significant anticonvulsant effect of α-spinasterol in all the used seizure tests. In the i.v. PTZ test, statistically significant elevation was noted in case of the threshold for myoclonic twitches (doses of 0.1-1 mg/kg) and generalized clonus seizures (doses of 0.5 and 1 mg/kg) but not for tonic seizures. The studied TRPV1 antagonist also increased the threshold for tonic hindlimb extension in the MEST (doses of 0.5 and 1 mg/kg) and 6 Hz psychomotor seizure (doses of 0.1 and 0.5 mg/kg) tests in mice. Furthermore, α-spinasterol did not produce any significant impairment of motor coordination (assessed in the chimney test) and muscular strength (investigated in the grip-strength test) and it did not provoke significant changes in body temperature in mice. Based on the results of our study and the fact that α-spinasterol is characterized by good blood-brain permeability, we postulate further investigation of this compound to precisely evaluate mechanism of its anticonvulsant action and opportunity of its usage in clinical practice.
authors.affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL 20-033, Lublin, Poland, ksocala@op.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Socała
authors.forename: Dorota
authors.initials: D
authors.lastname: Nieoczym
authors.forename: Mateusz
authors.initials: M
authors.lastname: Pieróg
authors.forename: Piotr
authors.initials: P
authors.lastname: Wlaź
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D010433:Pentylenetetrazole; D011897:Random Allocation; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C031312:spinasterol; D013265:Stigmasterol; D010433:Pentylenetetrazole