Pancuronium bromide: an indirect sympathomimetic agent

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Neuropharmacology

Background:

• Pancuronium is a neuromuscular blocking agent.
• Its cardiovascular effects are not fully understood.
• Previous studies suggest potential interactions with the sympathetic nervous system.

Purpose of the Study:

• To investigate the mechanism of pancuronium-induced pressor responses in dogs.
• To determine if pancuronium releases noradrenaline.
• To explore the role of the sympathetic nervous system in pancuronium's cardiovascular effects.

Main Methods:

• Administered pancuronium (0.2 mg/kg) to dogs and monitored cardiovascular parameters (left ventricular systolic pressure, systemic arterial pressure, central venous pressure).
• Investigated tachyphylaxis to pancuronium and its restoration.
• Utilized noradrenaline infusions and sympathetic blocking agents (desipramine, guanethidine, reserpine) to probe the underlying mechanisms.

Main Results:

• Pancuronium increased left ventricular systolic and systemic arterial pressures, with diminishing responses upon repeated dosing (tachyphylaxis).
• Pressor response to pancuronium was restored by intravenous noradrenaline infusion after tachyphylaxis.
• Sympathetic blocking agents (desipramine, guanethidine, reserpine) inhibited the restoration of the pressor response by noradrenaline.

Conclusions:

• Findings support the hypothesis that pancuronium induces a pressor response by triggering noradrenaline release from postganglionic nerve endings.
• The sympathetic nervous system plays a crucial role in mediating pancuronium's cardiovascular effects.
• Pancuronium's action involves interaction with noradrenergic neurotransmission.