Elsevier

Biomedicine & Pharmacotherapy

Volume 111, March 2019, Pages 882-890
Biomedicine & Pharmacotherapy

Interventional and preventive effects of aripiprazole and ceftriaxone used alone or in combination on oxaliplatin-induced tactile and cold allodynia in mice

https://doi.org/10.1016/j.biopha.2019.01.008Get rights and content
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Highlights

  • In mice aripiprazole and ceftriaxone attenuate oxaliplatin-induced tactile allodynia.

  • These drugs do not reduce cold allodynia caused by oxaliplatin.

  • Repeated-dose ceftriaxone inhibits the development of late-phase tactile allodynia.

  • Aripiprazole but not ceftriaxone markedly affects motor functions of mice.

  • Locomotor activity of neuropathic mice is also significantly reduced by aripiprazole.

Abstract

Background and purpose

Chemotherapy-induced peripheral neuropathy (CIPN) is a pharmacoresistant neurological complication induced by some antitumor drugs. This study aimed to assess antiallodynic properties of aripiprazole and ceftriaxone used alone or in combination to attenuate neuropathic pain related to CIPN caused by oxaliplatin.

Methods

Neuropathic pain was induced in mice by a single intraperitoneal dose of oxaliplatin (10 mg/kg). Aripiprazole and ceftriaxone were used in a single- or repeated dosing protocol. Their antiallodynic activity was assessed using von Frey and cold plate tests on the day of oxaliplatin injection and after 7 days. The influence of aripiprazole and ceftriaxone on animals’ locomotor activity and motor coordination was also assessed.

Results

Single-dose and repeated-dose aripiprazole 10 mg/kg and ceftriaxone 200 mg/kg used alone and in combination attenuated early-phase and late-phase tactile allodynia in oxaliplatin-treated mice. Repeated administrations of ceftriaxone 200 mg/kg prevented the development of late-phase tactile allodynia. Both drugs showed no antiallodynic properties in the cold plate test. Single-dose aripiprazole 1 and 10 mg/kg but not its repeated administration significantly decreased locomotor activity of oxaliplatin-treated mice. Single-dose aripiprazole 1 and 10 mg/kg, aripiprazole 1 mg/kg + ceftriaxone 50 mg/kg and aripiprazole 1 mg/kg + ceftriaxone 200 mg/kg impaired motor coordination in the rotarod test.

Conclusions

In mice, neither ceftriaxone nor aripiprazole attenuated cold allodynia. Ceftriaxone alone could attenuate tactile allodynia caused by oxaliplatin without inducing motor adverse effects. Although the administration of aripiprazole reduced tactile allodynia, this effect seems to be limited considering severe motor deficits induced by this drug.

Abbreviations

CIPN
chemotherapy-induced peripheral neuropathy
CDT
combination drug therapy
GLT-1
glutamate transporter isoform 1

Keywords

Oxaliplatin
Chemotherapy-induced peripheral neuropathy
Aripiprazole
Combination drug therapy
Ceftriaxone
Allodynia

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