title: The systemic toxicity of equipotent proxymetacaine, oxybuprocaine, and bupivacaine during continuous intravenous infusion in rats.
abstract: BACKGROUND
  Although proxymetacaine and oxybuprocaine produce topical ocular and spinal anesthesia, they have never been tested as cutaneous anesthetics. We compared cutaneous analgesia of proxymetacaine and oxybuprocaine with bupivacaine and tested their central nervous system and cardiovascular toxicity.
  
  
  METHODS
  After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the local anesthetic effect of proxymetacaine and oxybuprocaine on cutaneous analgesia in rats. After i.v. infusions of equipotent doses of oxybuprocaine, proxymetacaine, and bupivacaine, we observed the onset time of seizure, apnea, and impending death and monitored mean arterial blood pressure and heart rate.
  
  
  RESULTS
  Proxymetacaine and oxybuprocaine acted like bupivacaine and produced dose-related cutaneous analgesia. On a 50% effective dose basis, the ranks of potencies were proxymetacaine > oxybuprocaine > bupivacaine (P < 0.01). Under equipotent doses, the infusion times of proxymetacaine or oxybuprocaine required to cause seizure, apnea, and impending death were longer than that of bupivacaine (P < 0.05). The decrease in mean arterial blood pressure and heart rate was slower with oxybuprocaine and proxymetacaine compared with bupivacaine (P < 0.05 for the differences) at equipotent doses.
  
  
  CONCLUSIONS
  Oxybuprocaine and proxymetacaine were more potent at producing cutaneous anesthesia but were less potent than bupivacaine at producing central nervous system and cardiovascular toxicity.
authors.affiliation: Department of Physical Therapy, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Liu
authors.forename: Dong-Zi
authors.initials: DZ
authors.lastname: Shao
authors.forename: Kuang-I
authors.initials: KI
authors.lastname: Cheng
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Chen
mesh_terms: D000698:Analgesia; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D020258:Neurotoxicity Syndromes / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D011343:Procaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D011430:Propoxycaine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced
chemical_list: D000779:Anesthetics, Local; D011343:Procaine; C005298:benoxinate; C005717:proxymetacaine; D011430:Propoxycaine; D002045:Bupivacaine