Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.

Abstract

Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.

• Authors: Oliver Linsell, Philip W Brownjohn, Hayley Nehoff, Khaled Greish, John C Ashton
• Journal: Journal of drug targeting (J Drug Target) Vol. 23 Issue 4 Pg. 353-9 (May 2015) ISSN: 1029-2330 [Electronic] England
• PMID: 25541465 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Analgesics
• Benzoxazines
• Maleates
• Micelles
• Morpholines
• Naphthalenes
• Polystyrenes
• styrene-maleic acid polymer
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone

Topics

• Analgesics (administration & dosage, pharmacokinetics, pharmacology)
• Animals
• Benzoxazines (administration & dosage, pharmacokinetics, pharmacology)
• Biological Transport
• Blood-Brain Barrier (metabolism)
• Disease Models, Animal
• Half-Life
• Hyperalgesia (drug therapy)
• Male
• Maleates (chemistry)
• Micelles
• Morpholines (administration & dosage, pharmacokinetics, pharmacology)
• Naphthalenes (administration & dosage, pharmacokinetics, pharmacology)
• Neuralgia (drug therapy)
• Polystyrenes (chemistry)
• Rats
• Rats, Wistar
• Sciatic Neuropathy (drug therapy)
• Time Factors