Metoclopramide attenuates iminodipropionitrile-induced oxidative stress and neurobehavioral toxicity in rats.
Author: Ahmad Khan H, Al Deeb S, Al Moutaery K, Tariq M.
Source:
Pharmacology Biochemistry and Behavior, 79(3), 555-561.
Metoclopramide (MET) has long been used as a neuroleptic and antiemetic drug in
clinical practice. Motor impairment and dyskinesia have been reported in some
patients following chronic treatment with MET. Occasionally, the adverse symptoms
may appear even after acute exposure to MET in more susceptible population (such
as elderly individual) or due to concomitant exposure to MET and certain
neurotoxins. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been
shown to produce dyskinetic syndrome in rodents. This study reports the effect of
concomitant exposure of rats to MET and IDPN on behavioral abnormalities in rats
namely excitation, circling and chorea (ECC) syndrome. Four groups of female
Wistar rats (aged 3 months) were given MET (0, 10, 40 and 80 mg/kg, i.p., for 11
days) 30 min before IDPN (100 mg/kg, i.p. for 8 days). Two additional groups of
rats were treated with either saline (control group) or 80 mg/kg of MET (drug
alone group). The animals were observed for neurobehavioral abnormalities
including dyskinetic head movement, circling, tail hanging, air righting reflex
and contact inhibition of righting reflex. Horizontal and vertical locomotor
activities and fore limbs grip strength were also measured. On day 12, the
animals were sacrificed and brains were collected for biochemical analysis. MET
significantly and dose-dependently protected the animals against IDPN-induced ECC
syndrome, motor impairment and deficiency in grip strength. MET also protected
the animals against IDPN-induced oxidative stress.