Cocaine abuse causes autonomic and cardiovascular effects that may be
life threatening. Attenuation of cocaine-induced seizures has been pro
duced by the noncompetitive antagonist of the N-methyl-D-aspartate rec
eptor channel complex, dizocilpine. The purpose of the present study w
as, first, to determine effects of dizocilpine on the incidence of pac
ing-induced ventricular arrhythmias and, second, to evaluate the effec
ts of dizocilpine on cocaine-induced depression of sympathetic efferen
t activity to the heart. Adult dogs were anesthetized and instrumented
for blood pressure and an electrocardiogram. After vagotomy and thora
cotomy, electrodes and strain gauges were sutured onto the right atriu
m and ventricle. A left thoracic sympathetic efferent nerve was isolat
ed and stimulated for analysis of the innervation pattern. Arrhythmias
were induced with programmed electrical stimulation of the heart befo
re and during left cardiac sympathetic efferent nerve stimulation. The
control incidence of induced arrhythmias was only 2%, which increased
to 21% during left sympathetic stimulation. Cocaine (2 mg/kg iv) sign
ificantly increased these to 11 and 42%, respectively. Dizocilpine (0.
5 mg/kg iv) reduced the incidence of induced ventricular arrhythmias t
o 2% with cocaine (P < 0.05) and to 19% with cocaine and left sympathe
tic stimulation (P < 0.01). One or two sympathetic efferent cardiac ne
rves were stimulated to evaluate innervation patterns. These nerves we
re severed and prepared for recording multifiber efferent neurograms.
Nerve traffic was analyzed by counting positive spikes for 15 s. Contr
ol activities were normalized at 100%. Within 6 min, cocaine (2 mg/kg
iv) reduced the sympathetic efferent activity to 83 +/- 4% of control
(n = 14 nerves). After at least 60 min of recovery, dizocilpine (0.5 m
g/kg iv) was given. A second administration of cocaine reduced the sym
pathetic efferent activity to only 94 +/- 3% of control. This is signi
ficantly (P < 0.02) less than the initial depression. In another group
of dogs pretreatment with dizocilpine before cocaine prevented the co
caine-induced depression in sympathetic efferent activity to the heart
(n = 16 nerves). Thus the proarrhythmic effects of cocaine and cocain
e-induced sympathetic efferent depression to the heart are attenuated
by the dizocilpine.