Study of the effect of some anticonvulsants on monamine mediated behavior in mice

In this study, the effects of carbamazepine, diazepam, phenytoin and valproic acid on 5-hydroxytryptophan [5-HTP] induced head twitch behavior in mice were evaluated. Moreover the effects of these anticonvulsants on apomorphine induced locomotion and clonidine-induced sedation were investigated. Data revealed that repeated administration of carbamazepine [20mg/kg i.p. once daily] diazepam [1.25 mg/kg i.p. twice daily] and valproic acid [400 mg/kg i.p. twice daily] for 14 days enhanced the 5-HTP [100 mg/kg i.p.] induced head twitch behavior. Carbamazepine enhancement of head twitch response may be due to an increase of 5-hydroxytryptamine [5-HT] receptor density. The effect of both diazepam and valproic acid was explained by their effects on gamma-aminobutyric acid [GABA] which alters 5-HT release. However phenytoin [40 mg/kg i.p. once daily for 14 days] was devoid of an effect on 5 -HTP induced head twitch behavior. The locomotion data showed that carbamazepine, diazepam, phenytoin and valproic acid were unable to alter apomorphine [1 mg/kg] induced locomotion. However, this effect may be due to that these drugs did not affect dopamine metabolism. Results of cloridine [0.15 mg/kg] induced sedation revealed that only valproic acid attenuated the clonidine-induced sedation. An effect which can be explained by its ability to decrease noradrenaline turnover

Study of the effect of phenobarbital and propylthiouracil on glutathione s-transferase in liver cytosol of rat

In this study three groups of rats were used. The first group was used as control and injected with saline, the second group was treated with PB [80 mg/kg I.P.] and the third group was given PTU [1.5 m mole/kg I.P.] after the end of treatment period [15 days], glutathione S-transferase was determined spectrophotometrically using Habig et al. 1974 method. Results revealed that both PB and PTU treatments increased the activity of GSH-S-transferase in vivo. However, PTU inhibited GSH-S-transferase in vitro. This inhibition was from 6.2 to 27.5% for 0.5 to 10 mM PTU respectively. Thus, there was a discrepancy between the in vivo and in vitro effects of PTU on GSH-S-transferase. This discrepancy was explained by that PTU activated some isoenzymes of GSH-S-transferase in vivo and inhbited other isoenzymes in vitro. The evaluated kinetic parameters revealed that the V max in n moles/min./mg protein of control, PB treated and PTU treated rats were 1176, 1818 and 1538 respectively. Thus PB was proved to be a potent inducer of GSH-S-transferase than PTU. The determined Km values for control, PB treated and PTU treated animals were 0.051, 0.06 and 0.062. Both PB and PTU treatments insignificantly affected the Km value of GSH-S-transferase. Thus the nature of enzyme affinity to substrate was not affected. i.e. the increase in GSH-S-transferase activity might be due to an increase of enzyme synthesis