The phthalimide analogues N-3-hydroxypropylphthalimide and N-carboxymethyl-3-nitrophthalimide exhibit activity in experimental models of inflammatory and neuropathic pain.

Abstract

BACKGROUND:

Phthalimide analogues devoid of the glutarimide moiety exhibit multiple biological activities, thus making them candidates for the treatment of patients with different diseases, including those with inflammatory and painful disorders. In the present study, the activities of five phthalimide analogues devoid of the glutarimide moiety (N-hydroxyphthalimide, N-hydroxymethylphthalimide, N-3-hydroxypropylphthalimide, N-carboxy-3-methylphthalimide, N-carboxymethyl-3-nitrophthalimide) were evaluated in experimental models of acute and chronic inflammatory and neuropathic pain.

METHODS:

The phthalimide analogues were administered per os (po) in Swiss mice or Wistar rats. Nociceptive response induced by formaldehyde and mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve or intraplantar (ipl) injection of complete Freund's adjuvant (CFA) were used as experimental models of pain.

RESULTS:

N-carboxymethyl-3-nitrophthalimide (700 mg/kg, -1 h) inhibited the second phase of the nociceptive response induced by the intraplantar injection of formaldehyde in mice. N-3-hidroxypropylphthalimide (546 mg/kg, -1 h) inhibited both phases of the nociceptive response induced by formaldehyde. Treatment of rats with N-carboxymethyl-3-nitrophthalimide (700 mg/kg) or N-3-hydroxypropylphthalimide (546 mg/kg) inhibited the mechanical allodynia induced by CCI of the sciatic nerve or ipl injection of CFA in rats. Intraperitoneal administration of the opioid antagonist naltrexone (10 mg/kg, -1.5 h) attenuated the antinociceptive activity of N-carboxymethyl-3-nitrophthalimide (700 mg/kg) in the model of nociceptive response induced by formaldehyde.

CONCLUSIONS:

N-3-hydroxypropylphthalimide and N-carboxymethyl-3-nitrophthalimide, two phthalimide analogues devoid of the glutarimide moiety, exhibited activities in different experimental models of pain, including models of chronic inflammatory and neuropathic pain.

• Authors: Carla R A Batista, Adriana M Godin, Ivo S F Melo, Giovanna M E Coura, Tamires C Matsui, Marcela M G B Dutra, Ana Mercy S Brito, Wagner G Canhestro, Ricardo J Alves, Débora P Araújo, Ângelo de Fátima, Renes R Machado, Márcio M Coelho
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 71 Issue 6 Pg. 1177-1183 (Dec 2019) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 31669881 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Chemical References

• Analgesics
• Isoindoles
• Isoquinolines
• Narcotic Antagonists
• Phthalimides
• Formaldehyde
• phthalimide
• 3-nitrophthalimide
• Freund's Adjuvant
• N-hydroxyphthalimide
• N-hydroxymethylphthalimide

Topics

• Analgesics (pharmacology)
• Animals
• Disease Models, Animal
• Formaldehyde (pharmacology)
• Freund's Adjuvant (pharmacology)
• Hyperalgesia (drug therapy)
• Inflammation (drug therapy)
• Isoindoles (pharmacology)
• Isoquinolines (pharmacology)
• Male
• Mice
• Narcotic Antagonists (pharmacology)
• Neuralgia (drug therapy)
• Pain Measurement (methods)
• Phthalimides (pharmacology)
• Rats
• Rats, Wistar
• Sciatic Nerve (drug effects)