α-Spinasterol, a TRPV1 receptor antagonist, elevates the seizure threshold in three acute seizure tests in mice

Abstractα-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.

• Publication year

  2015

• Venue

  Journal of neural transmission

• Publication date

  2015-03-13

• Fields of study

  Medicine

• Identifiers
  DOI 10.1007/s00702-015-1391-7PMID 25764210PMCID 4540766
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2014influential reference
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  2014influential reference
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• Spices: the savory and beneficial science of pungency.

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• Polypeptide Modulators of TRPV1 Produce Analgesia without Hyperthermia

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  2012influential reference
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  2012influential reference
• TRPV1 Channels Regulate Cortical Excitability in Humans

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  2010influential reference
• The maximal electroshock seizure (MES) model in the preclinical assessment of potential new antiepileptic drugs.

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  2005cited by this paper
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  2001cited by this paper
• Neuropharmacology Methods in Epilepsy Research

  1998cited by this paper
• The capsaicin receptor: a heat-activated ion channel in the pain pathway

  1997cited by this paper
• Dose-dependent anticonvulsant and proconvulsant effects of nitric oxide synthase inhibitors on seizure threshold in a cortical stimulation model in rats.

  1995cited by this paper
• [Anti-inflammatory effect of alpha-spinasterol].

  1985cited by this paper
• [Anti-inflammatory effect of alpha-spinasterol].

  1985influential reference
• Chemical protection against ionizing radiation. I. Sampling methods for screening compounds in radiation protection studies with mice.

  1957cited by this paper
• On Chemical Protection against Ionizing Radiation

  1954cited by this paper

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