Pharmacological evaluation of the gabapentin salicylaldehyde derivative, gabapentsal, against tonic and phasic pain models, inflammation, and pyrexia.

Abstract

Gabapentinoids are effective drugs in most animal models of pain and inflammation with variable effects in humans. The current study evaluated the pharmacological activity of gabapentin (GBP) and its salicylaldehyde derivative (gabapentsal; [2-(1-(((2-hydroxybenzylidene) amino) methyl) cyclohexyl) acetic acid]; GPS) in well-established mouse models of nociceptive pain, inflammatory edema, and pyrexia at doses of 25-100 mg/kg. GPS allayed tonic visceral pain as reflected by acetic acid-induced nociception and it also diminished thermally induced nociception as a mimic of phasic thermal pain. Antagonism of GPS-induced antinociceptive activities by naloxone (NLX, 1.0 mg/kg, subcutaneously, s.c), beta-funaltrexamine (β-FNT, 5.0 mg/kg, s.c), naltrindole (NT, 1.0 mg/kg, s.c), and nor-binaltorphimine (NOR-BNI, 5.0 mg/kg, s.c), and pentylenetetrazole (PTZ-15 mg/kg, intraperitoneally, i.p) implicated an involvement of both opioidergic and GABAergic mechanisms. Tail immersion test was conducted in order to delineate the mechanistic insights of antinociceptive response. Inflammatory edema induced by carrageenan, histamine, or serotonin was also effectively reversed by GPS in a fashion analogous to aspirin (150 mg/kg, i.p), chlorpheniramine (1.0 mg/kg, i.p), and mianserin (1.0 mg/kg, i.p), respectively. Additionally, yeast-induced pyrexia was decreased by GPS in a comparable manner to acetaminophen (50 mg/kg, i.p). These observations suggest that GPS possesses ameliorative properties in tonic, phasic, and tail immersion tests of nociception via opioidergic and GABAergic mechanisms, curbs inflammatory edema, and is antipyretic in nature.

• Authors: Nisar Ahmad, Fazal Subhan, Nazar Ul Islam, Muhammad Shahid, Naseem Ullah, Rahim Ullah, Muhammad Khurram, Muhammad Usman Amin, Shehla Akbar, Ihsan Ullah, Robert D E Sewell
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 394 Issue 10 Pg. 2033-2047 (10 2021) ISSN: 1432-1912 [Electronic] Germany
• PMID: 34254154 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Aldehydes
• Analgesics
• Anti-Inflammatory Agents
• Antipyretics
• salicylaldehyde
• Serotonin
• Gabapentin
• Histamine
• Carrageenan

Topics

• Aldehydes (therapeutic use)
• Analgesics (therapeutic use)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antipyretics (therapeutic use)
• Carrageenan
• Disease Models, Animal
• Edema (chemically induced, drug therapy)
• Fever (drug therapy)
• Gabapentin (analogs & derivatives, therapeutic use)
• Histamine
• Male
• Mice, Inbred BALB C
• Nociceptive Pain (drug therapy)
• Saccharomyces cerevisiae
• Serotonin