Reversal Effects of Neostigmine, Edrophonium and 4-aminopyridine of Verapamil Pretreatment on Pipecuronium Induced Neuromuscular Blockade in Rat-Hemidiaphragm

Park, Jung Won; Yoon, Suk Min

Abstract

BACKGROUND: It has been shown that L-type calcium channel blockers increase the muscle relaxation effects of non-depolarizing neuromuscular blocking agents whereas the potentiated neuromuscular blocking effects by L-type calcium channel blocker are resistant to reversal by neostigmine. The aims of this study were 1) to see whether the pretreatment of L-type calcium channel blocker, such as verapamil, aggravates the pipecuronium-induced muscle relaxation, 2) if so, to see whether these effects are reversed by anticholinesterase, such as neostigmine and edrophonium or potassium channel blocker, such as 4-aminopyridine.
METHODS
The rat-phrenic nerve-hemidiaphragms (n=60) were prepared. Twenty microgram of pipecuronium was administered to all organ bath. All samples were divided into two groups according to the administration of 10uM of verapamil i.e. verapamil pretreated, non-pretreated group. The amounts of administered pipecuronium were gradually increased by 4ug until the force of twitch decreased to 10% of control value in both groups. Each group was subdivided into three groups according to the administration of 0.75 M of neostigmine, 12.4 uM of edrophonium or 40uM of 4-aminopyridine.
RESULTS
The dose of pipecuronium required for the decrease of contractile force to 10% of control value was less in verapamil pretreated group than in non-pretreated group. And, the decrease of contractile force in both groups was more effectively reversed by 4-aminopyridine than neostigmine and edrophonium.
CONCLUSIONS
Verapamil potentiates the pipecuronium-induced neuromuscular blockade and 4-aminopyridine is more effective to reverse verapamil pretreated, pipecuronium induced neuromuscular blockade.