Acute in vitro neuromuscular effects of carbamazepine and carbamazepine-10,11-epoxide.
We examined the acute neuromuscular effects of the anticonvulsant, carbamazepine, and its major metabolite, carbamazepine-10,11-epoxide, using the in vitro rat phrenic nerve-hemidiaphragm muscle preparation. Carbamazepine produced 8.8% +/- 2.2% (n = 12) neuromuscular paralysis as its concentration was increased from 1 to 50 microg/mL (4.2-210 microM). In contrast, carbamazepine-10,11-epoxide produced maximum paralysis of 65% +/- 8% (n = 10) in the concentration range 1-100 microg/mL (4-400 microM) and the concentration required to produce half this paralysis was 36 +/- 7 microg/mL (144 +/- 28 microM). Carbamazepine 10 microg/mL (42 microM) shifted the response-concentration curve for both a depolarizing (succinylcholine) and a nondepolarizing (atracurium) neuromuscular blocker, reducing their concentrations required for 50% paralysis by approximately 30%. In contrast, the metabolite, which was a more potent neuromuscular blocker by itself, failed to alter either succinylcholine or atracurium effect. These results concur with previous clinical reports where anticonvulsants have acutely reduced neuromuscular blocker dose requirements.
Nguyen
A
A
Department of Pharmacy, The University of Sydney, New South Wales, Australia.
Ramzan
I
I
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide