Effect of diazepam on the state of Na, K-Atpase in a cortical focus of hyperactivity induced by penicillin

Excessive release of glutamate can cause many nervous system disorders. It has been reported that when a high dose of penicillin sodium is administered into the rat's brain, epilepsy, accompanied with glutamate elevation, will result. In this experiment, a low dose of penicillin sodium (1000 kIU/l) was microinjected into the rat's lateral ventricle to set up an overexcitation model, in which the concentration of ipsilateral hippocampal glutamate was monitored in vivo. by microdialysis-HPLC method as an indicator of the rat's excitatory state. Influences of sedative-hypnotic drugs on this model were verified by coadministration of diazepam or phenobarbital with Na-PCN intracerebroventricularly. In models, hippocampal glutamate concentration was elevated to 307% compared with its baseline level (p < 0.05), and this increase of glutamate was inhibited completely when different doses of diazepam or phenobarbital were administered (p < 0.05). The sedative effect of jujuboside A and trifluoperazine were then studied with this model. Jujuboside A (JuA) 0.1 g/l also reduced the glutamate level significantly (p < 0.05). Calmodulin antagonist trifluoperazine showed similar inhibitory effect as JuA, which may indicate that the effect of JuA is correlated with its anticalmodulin action. This model can be used to investigate the inhibitory effect of central nervous system drugs.

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Application of Overexcitation Model Induced by Penicillin Sodium in the Study of Inhibitory Effect of Sedative-Hypnotic Drugs

Yingjun

Zhang

Shou

et al. 2005

Pharmaceutical Biology

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Selective inhibition of brain Na,K-ATPase by drugs

Horvat

Momić²,

Petrović³

et al. 2006

Physiol Res

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The effect of drugs from the class of cardiac (methyldigoxin, verapamil, propranolol), antiepileptic (carbamazepine), sedative (diazepam) and antihistaminic (promethazine) drugs on Na,K-ATPase activity of plasma membranes was studied in rat brain synaptosomes. Methyldigoxin in a concentration of 0.1 mmol/l inhibits enzyme activity by 80 %. Verapamil, propranolol and promethazine in concentrations of 20, 20 and 2 mmol/l respectively, entirely inhibit the ATPase activity. Carbamazepine and diazepam in concentrations of 0.02-60 mmol/l have no effect on the activity of this enzyme. According to the drug concentrations that inhibit 50 % of enzyme activity (IC(50)), the potency can be listed in the following order: methyldigoxin promethazine verapamil ? propranolol. From the inhibition of commercially available purified Na,K-ATPase isolated from porcine cerebral cortex in the presence of chosen drugs, as well as from kinetic studies on synaptosomal plasma membranes, it may be concluded that the drugs inhibit enzyme activity, partly by acting directly on the enzyme proteins. Propranolol, verapamil and promethazine inhibitions acted in an uncompetitive manner. The results suggest that these three drugs may contribute to neurological dysfunctions and indicate the necessity to take into consideration the side effects of the investigated drugs during the treatment of various pathological conditions.

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Tramadol Effects on the Activity Levels of ATPases in Mitochondrial Fractions of Rat Brain Areas During Non-Induction of Pain

Chetan¹,

Ramakrishna²,

.³

et al. 2007

International J. of Pharmacology

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Effect of diazepam on the state of Na, K-Atpase in a cortical focus of hyperactivity induced by penicillin

Cited by 3 publications

References 11 publications

Application of Overexcitation Model Induced by Penicillin Sodium in the Study of Inhibitory Effect of Sedative-Hypnotic Drugs

Application of Overexcitation Model Induced by Penicillin Sodium in the Study of Inhibitory Effect of Sedative-Hypnotic Drugs

Selective inhibition of brain Na,K-ATPase by drugs

Tramadol Effects on the Activity Levels of ATPases in Mitochondrial Fractions of Rat Brain Areas During Non-Induction of Pain

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