Isobolographic Analysis of Epinephrine With Bupivacaine, Dextromethorphan, 3-Methoxymorphinan, or Dextrorphan on Infiltrative Anesthesia in Rats: Dose-Response Studies

Chen, Yu Wen; Liu, Kuo Sheng; Wang, Jhi Joung; Chou, Willy; Hung, Ching Hsia

doi:10.1016/j.rapm.2007.08.012

Cited by 11 publications

(28 citation statements)

References 25 publications

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“…channel blockers. 2 They both produce spinal anesthesia, 3 sciatic nerve blockade, 4 and infiltrative cutaneous anesthesia 5,6 in rats. We found that dextromethorphan and dextrorphan, as local anesthetics, were more potent than lidocaine, 5 and the spinal blockade caused by dextrorphan was similar to that of bupivacaine.…”

Section: Discussionmentioning

confidence: 99%

“…Subcutaneous injections of drugs were administered as reported previously. 5,6,15 Briefly, the drugs, which were dissolved in normal saline 0.6 mL, were injected subcutaneously in non-anesthetized rats using a 30-G needle on the dorsal surface of the thoracolumbar region. The back of each rat was divided into left and right parts, either of which received one drug injection with a washout period of one week.…”

Section: Part I -Infiltrative Cutaneous Anesthesiamentioning

confidence: 99%

“…The cutaneous anesthetic effects of the drugs were evaluated using the cutaneous trunci muscle reflex, which is characterized by the reflex movement of the skin over the back produced by twitches of the lateral thoracispinal muscle in response to local dorsal cutaneous stimulation. 5,6,15 A No.15 von Frey filament (Somedic Sales AB, Stockholm, Sweden) affixed with the cut end of an 18-G needle was used to produce the standardized nociceptive stimulus (19 ± 1 g). Six pinpricks (at six different points within each wheal) with a frequency of 0.5-1 Hz were used in each testing.…”

Section: Part I -Infiltrative Cutaneous Anesthesiamentioning

confidence: 99%

“…The drug duration of action was defined as the time from drug injection (i.e., time = 0) to full recovery (no analgesic effect or 0% PE recorded). 5,6,15 After subcutaneously injecting the rats with four different doses of each drug (n = 8 for each dose of each drug), cutaneous anesthesia was plotted against time. The lower doses were tested first, and then larger doses were given until comparable doses of each drug were obtained.…”

Section: Part I -Infiltrative Cutaneous Anesthesiamentioning

confidence: 99%

“…3,4 Moreover, dextromethorphan and dextrorphan are potent local anesthetics with a therapeutic index in animals (50% lethal dose/50% effective dose) 2.4-and 1.9-fold greater, respectively, than lidocaine when used for cutaneous anesthesia. 5,6 Using either dextromethorphan or dextrorphan for cutaneous anesthesia 5,6 and sciatic nerve blockade 4 produces a longer effect than lidocaine, and spinal blockade using dextrorphan is similar in duration as bupivacaine, 3 a long-acting local anesthetic. Thus, the suitability of these drugs as clinical local anesthetics is worth further evaluation.…”

mentioning

confidence: 99%

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Systemic dextromethorphan and dextrorphan are less toxic in rats than bupivacaine at equianesthetic doses

Chen

Wang

Liu

et al. 2010

Can J Anesth/J Can Anesth

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Purpose Dextrorphan, a major metabolite of dextromethorphan, produces the duration of spinal and cutaneous anesthesia similar to bupivacaine. The purpose of this study was to test the central nervous system and cardiovascular toxicity of bupivacaine, dextromethorphan, and dextrorphan. Methods First, dose-response curves for dextromethorphan, dextrorphan, and bupivacaine (n = 8 at each testing point) were determined for cutaneous analgesia on the rat back, and equipotent doses were calculated. Next, during continuous intravenous infusion of equipotent doses of bupivacaine, dextromethorphan, and dextrorphan (n = 8 in each group), we observed the time to seizure, apnea, and complete cardiac arrest. A saline group (n = 7) was used for comparison. Mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV), and cardiac output (CO) were also monitored. Results Bupivacaine, dextromethorphan, and dextrorphan produced dose-dependent cutaneous anesthesia. A longer duration of equipotent infusion doses was required to produce seizures in the dextromethorphan group (10.6 ± 1.3 min) than in the bupivacaine group (7.6 ± 2.1 min) (P = 0.005). Dextrorphan did not produce any seizures. Compared with bupivacaine, time to apnea and complete cardiac arrest was longer with dextrorphan (P \ 0.001) and with dextromethorphan (P = 0.001). Cardiovascular collapse, defined as a decline in MAP, HR, CO, and SV, was slower in the dextromethorphan and dextrorphan groups than in the bupivacaine group (P \ 0.001 for both comparisons). Conclusion At equipotent doses for local anesthesia, dextromethorphan and dextrorphan were less likely than bupivacaine to induce central nervous system and cardiovascular toxicity. RésuméObjectif Le dextrorphane, un me´tabolite majeur du dextrome´thorphane, produit une anesthe´sie rachidienne et cutane´e d'une dure´e similaire a`la bupivacaı¨ne. L'objectif de cette e´tude consistait a`e´valuer la toxicite´de la bupivacaı¨ne, du dextrome´thorphane et du dextrorphane sur le syste`me nerveux central et le syste`me cardiovasculaire. Méthode Tout d'abord, les courbes dose-re´ponse du dextrome´thorphane, du dextrorphane et de la bupivacaı¨ne (n = 8 pour chaque essai) ont e´te´de´termine´es pour l'analge´sie cutane´e sur le dos du rat, et des doses Y.W. Chen and Y.C. Chen contributed equally to this study.

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