Abstract | BACKGROUND: METHODS: Male Sprague-Dawley rats were randomly divided into six groups (n = 8, each group). Rats were pretreated with intracerebroventricular saline (cerebroventricle-control: CV-C group), 10 or 30 microg/kg of (S)-(-)- propranolol ( propranolol) (cerebroventricle-small dose: CV-S and cerebroventricle-large dose: CV-L groups, respectively) or i.v. saline (IV-control: IV-C group), 1 or 3 mg/kg of propranolol (IV-small dose: IV-S and IV-large dose: IV-L groups, respectively). Three minutes later, lidocaine was administered i.v. at 4 mg x kg(-1) x min(-1) until tonic-clonic convulsions occurred. RESULTS: The convulsive dose of lidocaine in the CV-L group was significantly larger than that in the CV-C group (30.6 +/- 5.1 vs 23.5 +/- 2.2 mg/kg, respectively, P = 0.008). Plasma concentrations of total and protein-unbound lidocaine, concentrations of lidocaine in the brain at the onset of convulsions were also significantly higher in the CV-L group than those in the CV-C group (36.1 +/- 4.8 vs 26.0 +/- 3.8 microg/mL, 22.5 +/- 3.5 vs 13.7 +/- 2.6 microg/mL, 82.7 +/- 7.1 vs 57.3 +/- 5.7 microg/g, P < 0.001 for all). The convulsive dose, plasma concentrations of total and protein-unbound lidocaine, and brain lidocaine in the IV-L group were also significantly larger than those in IV-C group and comparable with those in the CV-L group. The plasma concentration of propranolol before starting an infusion of lidocaine in the IV-L group was approximately 60-fold higher than that in the CV-L group (554.7 +/- 104.6 and 9.3 +/- 6.7 ng/mL, respectively). CONCLUSIONS:
Propranolol increased the threshold for lidocaine-induced convulsions by directly acting on the brain.
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Authors | Taketo Nakamura, Yutaka Oda, Ryota Takahashi, Katsuaki Tanaka, Ichiro Hase, Akira Asada |
Journal | Anesthesia and analgesia
(Anesth Analg)
Vol. 106
Issue 5
Pg. 1450-5, table of contents
(May 2008)
ISSN: 1526-7598 [Electronic] United States |
PMID | 18420859
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic beta-Antagonists
- Anesthetics, Local
- Anticonvulsants
- Lidocaine
- Propranolol
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Topics |
- Adrenergic beta-Antagonists
(administration & dosage, blood, pharmacology)
- Anesthetics, Local
(administration & dosage, blood, toxicity)
- Animals
- Anticonvulsants
(administration & dosage, blood, pharmacology)
- Brain
(drug effects, metabolism)
- Dose-Response Relationship, Drug
- Drug Interactions
- Hemodynamics
(drug effects)
- Infusions, Intravenous
- Injections, Intraventricular
- Lidocaine
(administration & dosage, blood, toxicity)
- Male
- Propranolol
(administration & dosage, blood, pharmacology)
- Protein Binding
- Rats
- Rats, Sprague-Dawley
- Seizures
(chemically induced, prevention & control)
- Wakefulness
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