Clonidine does not affect lidocaine seizure threshold in rats.
We investigated the effect of clonidine on intravenous (i.v.) lidocaine-induced haemodynamic changes and convulsions in awake rats. Wistar rats (200-250 g) were divided into three groups of eight and were pretreated with i.v. clonidine or normal saline 15 min before lidocaine infusion. Group 1 received normal saline; Group 2, 1 microgram.kg-1 clonidine; and Group 3, 10 micrograms.kg-1 clonidine. After surgical preparation and recovery from anaesthesia, all groups received a continuous i.v. infusion of lidocaine (15 mg.ml-1) at a rate of 4 mg.kg-1.min-1 until generalized convulsions occurred. Oxygenation was well maintained in all groups. Pretreatment with clonidine changed neither cumulative convulsant doses (Group 1: 41.8 +/- 2.2, Group 2: 43.8 +/- 2.6, Group 3: 42.3 +/- 2.0 mg.kg-1, respectively) nor plasma concentrations of lidocaine at the onset of convulsions (Group 1: 10.5 +/- 0.3, Group 2: 10.8 +/- 0.3, Group 3: 10.6 +/- 0.3 micrograms.ml-1, respectively). The mean arterial blood pressures in Groups 2 and 3 were decreased after clonidine pretreatment (Group 2: 93 +/- 1, P < 0.01, Group 3: 90 +/- 1%, P < 0.01, respectively) and they gradually increased during lidocaine infusion. The heart rates decreased after clonidine pretreatment (Group 2: 94 +/- 2, P < 0.05, Group 3: 86 +/- 2%, P < 0.01, respectively) and the combination of clonidine and lidocaine potentiated the bradycardic effect of lidocaine at a subconvulsant dose. Our results indicate that clonidine has neither anticonvulsant nor proconvulsant effects on lidocaine-induced convulsions. However, the interactions of clonidine and lidocaine on blood pressure and heart rate should be investigated further.
Yokoyama
M
M
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Japan.
Hirakawa
M
M
Goto
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008012:Lidocaine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013997:Time Factors
D002245:Carbon Dioxide; D008012:Lidocaine; D003000:Clonidine; D010100:Oxygen