Abstract
Introduction: The article presents the results of the study of the maximum tolerant dose (MTD) and the analgesic activity of peptide PT1 isolated from Alopecosa marikovskyi spider venom. PT1 is the first compound of polypeptide nature, capable of exerting a selective modulating effect on purinergic P2X3 receptors.
 Materials and methods: The study was conducted on 174 ICR mice. The analgesic activity of the peptide was evaluated in a thermal hypersensitivity test triggered by CFA and in a model of chemical irritation.
 Results and discussion: The determined MTD for the peptide PT1 when administered intravenously provides evidence to attribute it to low-toxic compounds. The maximum analgesic activity of PT1 using the biomodel of hypersensitivity induced by CFA when tested 15 minutes after the administration was recorded at doses of 0.1 and 0.5 mg/kg. In the visceral pain test, the maximum analgesic activity 15 minutes after the administration of the chemical stimulus was observed at a dose of 0.01 mg/kg.
 Conclusions: According to the results of testing peptide PT1, it is shown that it belongs to low-toxic compounds, has a pronounced analgesic activity in a wide range of doses of 0.0001–10 mg/kg.
Highlights
The article presents the results of the study of the maximum tolerant dose (MTD) and the analgesic activity of peptide PT1 isolated from Alopecosa marikovskyi spider venom
The study of MTD of the PT1 peptide after intravenous administration was started with a dose of 50 mg/kg, and further the dose was increased, since no death of the experimental animals was observed
The maximum analgesic activity of PT1 using the biomodel of hypersensitivity triggered by CFA in tests 15 minutes after the administration was recorded at doses of 0.1 and 0.5 mg/kg
Summary
Nowadays pain is one of the main reasons for seeking medical help. The perception of pain is an important protective ability of the body, informing us of the harmful effects that damage tissues and organs or pose a potential danger to the body. Palikova YuA et al.: Maximum tolerant dose and analgesic activity of PT1 peptide. Localized, and after a few seconds, it is replaced by diffuse, less acute and more emotionally colored Such dynamics of pain is associated with the participation of various afferent systems in conducting nociceptive impulses (Al Darwish Alopecosa marikovskyi et al 2016, Dyachenko et al 2018, Palikova et al 2018a, Palikova et al 2018b, Sharkey 2013, Sharma et al 2015). In 2012, in a targeted search for natural analgesic compounds in the laboratory of neuroreceptors and neuroregulators of the IBCh RAS from the Central Asian wolf spider, purotoxin PT1, a peptide that inhibits one of the most important subtypes of human pain receptors was isolated and comprehensively characterized. It was shown that PT1 in nanomolar concentrations significantly reduces ATP receptor activation, stabilizing the receptor desensitization stage (Grishin et al 2010)
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