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Background.Safe sensory-selective local anesthetics would be a major advance in the management of acute and chronic pain. Here we describe the sensory-selective local anesthetic properties and the toxicity profile of a known metabolite of amino-amide local anesthetics,2',6'-pipecolylxylidine (PPX). Methods.PPX was synthesized and made into its hydrochloride salt. PPX or ropivacaine (ROP) were injected at the sciatic nerve or intrathecally in rats, who then underwent modified hotplate (sensory) testing and weight-bearing (motor) testing. Rats injected with PPX or ROP were assessed for clinical toxicity endpoints. Conduction blockade was studied with single-unit recordings in mice. Biocompatibility was assessed histologically. Results.In male rats, sciatic sensory and motor block from 15 mM ROP lasted ~150 min; sensory nerve block from 30 mM PPX lasted 67.4 ± 17.4 min without motor block. Addition of chemical permeation enhancers to 30 mM PPX abolished sensory selectivity. Intrathecal 15 mM ROP produced sensory and motor block lasting ~15 min; sensory block from 30 mM PPX lasted 24.8 ± 8.7 min without motor block; repeated injection caused continuous sensory-selective block. In female rats, sciatic nerve blocks with ROP were similar to blocks in males, while blocks with PPX were sensory-selective but higher PPX concentrations were required. Ex vivo, 1.5 mM ROP caused reversible block of Aδ and C-fibers; 15 mM PPX blocked Aδ- but not C-fibers. Systemic 39.0 ± 1.8 mg/kg ROP caused severe clinical toxicity; 75.3 ± 3.2 mg/kg PPX caused none. Tissue reaction to PPX was benign, comparable to that of ROP. Conclusions.PPX provides sensory-selective local and neuraxial anesthesia with a good safety profile. The sensory selectivity may be attributable to the particular hydrophilic-hydrophobic balance of PPX.
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A systematic study of injectable anesthetic agents in the brown anole lizard ( Anolis sagrei )
Anolis lizards have served as important research models in fields ranging from evolution and ecology to physiology and biomechanics. However, anoles are also emerging as important models for studies of embryo development and tissue regeneration. The increased use of anoles in the laboratory has produced a need to establish effective methods of anesthesia, both for routine veterinary procedures and for research procedures. Therefore, we tested the efficacy of different anesthetic treatments in adult female Anolis sagrei. Alfaxalone, dexmedetomidine, hydromorphone, ketamine and tribromoethanol were administered subcutaneously (SC), either alone or combined at varying doses in a total of 64 female anoles. Drug induction time, duration, anesthesia level and adverse effects were assessed. Differences in anesthesia level were observed depending on injection site and drug combination. Alfaxalone/dexmedetomidine and tribromoethanol/dexmedetomidine were the most effective drug combinations for inducing a surgical plane of anesthesia in anoles. Brown anoles injected SC with alfaxalone (30 mg/kg) plus dexmedetomidine (0.1 mg/kg) or with tribromoethanol (400 mg/kg) plus dexmedetomidine (0.1 mg/kg) experienced mean durations of surgical anesthesia levels of 31.2 ± 5.3 and 87.5 ± 19.8 min with full recovery after another 10.9 ± 2.9 and 46.2 ± 41.8 min, respectively. Hydromorphone given with alfaxalone/dexmedetomidine resulted in deep anesthesia with respiratory depression, while ketamine/hydromorphone/dexmedetomidine produced only light to moderate sedation. We determined that alfaxalone/dexmedetomidine or tribromoethanol/dexmedetomidine combinations were sufficient to maintain a lizard under general anesthesia for coeliotomy. This study represents a significant step towards understanding the effects of anesthetic agents in anole lizards and will benefit both veterinary care and research on these animals.
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- PAR ID:
- 10525183
- Publisher / Repository:
- SAGE Publications
- Date Published:
- Journal Name:
- Laboratory Animals
- Volume:
- 54
- Issue:
- 3
- ISSN:
- 0023-6772
- Format(s):
- Medium: X Size: p. 281-294
- Size(s):
- p. 281-294
- Sponsoring Org:
- National Science Foundation
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