Spinal sensory and motor blockade by intrathecal doxylamine and triprolidine in rats

J Pharm Pharmacol. 2018 Dec;70(12):1654-1661. doi: 10.1111/jphp.13017. Epub 2018 Sep 25.

Abstract

Objectives: The aim of this experiment was mainly to examine the effects of intrathecally injected doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions.

Methods: After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with doxylamine or triprolidine were conducted.

Key findings: Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine > mepivacaine > doxylamine (P < 0.05) at provoking spinal motor, proprioceptive and nociceptive blockades. On the equianaesthetic doses (ED25 , ED50 and ED75 ), the duration of spinal anaesthesia with doxylamine was longer (P < 0.01) than that with mepivacaine or triprolidine. Moreover, doxylamine or triprolidine displayed greater potency (ED50 ) (P < 0.05) and duration (P < 0.05) of sensory block over motor block.

Conclusions: Doxylamine or triprolidine produces a dose-dependent effect of spinal motor and sensory block. Triprolidine with a better nociception-selective action over motor block has a better potency than mepivacaine or doxylamine. Doxylamine and triprolidine produce longer durations than mepivacaine.

Keywords: doxylamine; mepivacaine; nociception; spinal anaesthesia; triprolidine.

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Doxylamine / administration & dosage
  • Doxylamine / pharmacology*
  • Histamine Antagonists / administration & dosage
  • Histamine Antagonists / pharmacology*
  • Injections, Spinal
  • Male
  • Mepivacaine / pharmacology
  • Motor Activity / drug effects
  • Movement / drug effects
  • Nerve Block / methods*
  • Nociception / drug effects
  • Proprioception / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Triprolidine / administration & dosage
  • Triprolidine / pharmacology*

Substances

  • Anesthetics, Local
  • Histamine Antagonists
  • Triprolidine
  • Doxylamine
  • Mepivacaine