N-methyl-D-aspartate(NMDA) receptors have been the target of a large number of studies, and the field of research is still rapidly growing. Many in vivo and in vitro studies support the hypothesis that NMDA receptors contribute to the development and expression of epilepsy and play a pivotal role in induction of synaptic plasticity i.e. long-term potentiation (LTP). Decreasing glutamatergic neurotransmission pro-vides rational therapeutic approaches to epilepsy. Potent anticonvulsant effects are seen with the acute administration of NMDA antagonists in a wide range of animal models. NMDA receptors are important potential targets for the development of antiepileptic drugs. However, the early optimism regarding competitive NMDA recognition site antagonists as antiepileptic drug candidates has been tempered by the recognition that such antagonists have significant toxicities. Several other approaches to NMDA receptor blockade appear promising, including competitive antagonism at the glycine site and low-affinity channel blockade. In addition, there is interest in NMDA-associated polyamine-and redox sites but clearly further work is required to address this issue. Interestingly, molecular biology studies of NMDA receptor have revealed multiplicity in this receptor subtypes and NMDA receptor subunit, NR1 and NR2 represent heterogeneity in this receptor. Certain classes of NMDA receptor antagonists are selective for specific subunit combinations.This is an area with promising scope in future for pharmacological exploitation, for instance, designing antagonists that are selective for subunit combinations that might show an increased expression during epileptogenesis. There are, however, many important questions that remain only partly answered and probably many more surprises ahead.

Objective :The study was designed to investigate the pro-or anticonvulsant action of natbuphine using maximal electroshock (MES) test. An attempt was also made to determine the possible opioid receptor mechanism involved. Method : MES seizures were induced in mice via transauricular electrodes (60mA, 0.2 sec). Seizure severity was assessed by the duration of hindlimb extensor phase. Results : lntraperitoneal administration of nalbuphine resulted in a dose-dependent inhibition of the hindlimb extensor phase during the MES. This anticonvulsant effect was antagonized by naloxone, MR2266 and naltrindole. Conclusion :The results suggest that the anti-MES effect of nalbuphine is evoked by stimulation of mu, kappa and delta receptors, since the effect was attenuated by respective receptor antagonists.

Objective : To explore the immunomodulatory and antineoplastic action of toad skin extract (TSE) in experimental animals Methods: TSE was injected (s.c.) in male albino mice. Lymphocyte (blood and spleen) and macrophage count were done at different time intervals. To estimate phagocytic activity carbon clearance assay was performed in albino mice. Effect of TSE on T-cell rosette, chemotaxis of leucocyte, and macrophage migration was also studied in vitro. To study antineoplastic activity, TSE was injected (i.p.) in Ehrlich Ascites Carcinoma (EAC) bearing mice. Survival time and tumour cell growth (in vivo) were estimated. Results : TSE significantly increased lymphocyte (blood and spleen) and macrophage count. TSE significantly increased phagocytic activity and showed positive meutrophil chemotaxis in vitro. Enhanced inhibition of macrophage migration and T-cell rosette formation was observed due to TSE. TSE also increased survivial time of EAC bearing mice and inhibited tumour cell growth in vivo. Conclusion :All these observations indicate that TSE possesses immunomodulatory and antineoplastic activity in experimental animals.

Objectives : Present investigation was designed to know whether the reported hepatoprotective activity of aqueous extract of Andrographis paniculata (AP) can be used for delaying the onset of liver cancerous changes as well as the reversibility of tumorogenic condition in Swiss in breed male mice. Methods :The aqueous extract was given orally to the animals suffering from liver damage - ultimately leading to tumour, induced by hexachloro cyclohexane (BHC). The histopathology and the various biochemical constituents were monitored. The parameters like protein and liver marker enzyme SGPT, SGOT and alkaline phosphatase were analysed at different time intervals. Results : SGPT, SGOT and alkaline phosphatase were found to be significantly high and the protein concentrations were reduced in BHC treated animals.The liver marker enzymes were found to be lowered in animals which were supplemented with the AP extract. Protein levels which were found to decrease on BHC treatment have shown an increase with AP supplementation. Conclusion :These results further confirm the hepato-protective property of AP and its probable role in delaying the hepatic turnerogenic condition.

Objective: To study the antispasmodic activity of diclofenac per se and its combination with pitofenone and fenpiverinium. Method: The antispasmodic activity study was carried out against acetylcholine (10 - 640 ng ml-1)-induced concentrations on rat colon. Results: Acetylcholine (10 - 640ngml-1) induced a concentration - dependent contraction of the smooth muscle. In concentration of 9.4x1O-5 and 14.1 x10-5 mol L-1 diclofenac, a non-steroidal antiinflammatory agent shifted the concentration-response curve of acetylcholine to the right without suppressing the maximum, whereas diclofenac in higher concentration, 18.9x10-5 mol L-l induced unsurmountable blockade. Diclofenac (9.4x1O-5 mol L-1) potentiated antispasmodic activity of pitofenone (2.5x10-6 mol L-l) and fenpiverinium (2.3x10-8 mol L-l). Conclusion: The present study suggests that combination of diclofenac, pitofenone and fenpiverinium may prove to be an effective antispasmodic formulation.

Objectives: To study the antiepileptic effect of verapamil, nifedipine and diltiazem against MES in mice. Methods: MES was induced in mice by a Techno Electroconvulsometer (50m Amp, 0.1 sec. duration). The abolition or reduction of duration of tonic extension was considered as the index for antiepileptic effect. The animals were treated with calcium channel blockers alone and in combination with phenytoin sodium. Results: Verapamil, nifedipine and diltiazem produced no significant antiepileptic effect alone. Verapamil and nifedipine potentiated the antiepileptic effect of phenytoin sodium but diltiazem exerted no such potentiating effect. Conclusion: Dose of phenytoin sodium can be reduced in epileptic patients receiving verapamil or nifedipine for some other clinical conditions.

Objectives: To study (a) the effect of buspirone on chemically-induced seizures in mice and (b) the possible receptor mechanisms involved. Methods: Picrotoxin 8 mg/kg ip was used for inducing seizures in mice. The onset and duration of convulsions and recovery/ death were observed. Animals were also observed for different stages of convulsions and a severity score was assigned to them. Results: Buspirone (20 mg/kg po) potentiated PTX-induced convulsions and reversed the anticonvulsant effect of diazepam. Clonidine pretreatment protected against the pro-convulsive effects of buspirone. Mianserin exhibited an effect similar to that of buspirone. Conclusion: Buspirone exhibited pro-convulsive action on seizures induced with PTX in mice. The study suggests a role of central ((-adrenoceptor in such effects.

0bjective:To study the effect of serotonergic agents on the amphetamine induced sniffing, biting, grooming and repetitive head movements. Methods:Effect of pretreatment with parachlorophenylalanine, I-tryptophan,fluoxetine, (+)fenfluramine, buspirone, cyproheptadine and ianserin on amphetamine induced sniffing and biting (in rats) and grooming and repetitive head movements (in mice) were observed. Results: Latency to sniffing and biting was decreased by parachlorophenylalanine and increased by buspirone, I-tryptophan, fenfluramine and mianserin. Latency to grooming was increased by I-tryptophan, fenfluramine and fluoxetine and decreased by cyproheptadine, parachlorophenylalanine, mianserin and buspirone.The latency to repetitive head movements was reduced by I tryptophan, fenfluramine and increased by cyproheptadine, parachlorophenylalanine, mianserin and buspirone. Conclusion: Serotonergic agents modify amphetamine induced stereotypy. The serotonergic agents produce differential effects on different components of amphetamine stereotypy

0bjectives:To find out the effect of theobromine or aminotransferase enzyme activities in serum, heart and liver in rats. Methods: Theobromine in two doses was administered by oral gavage to albino Wistar rats (n=8 for each group) for a four day period and both alanine aminotransferase (AST) and aspartate aminotransferase (ALT) enzyme activities were measured in serum, heart and liver tissues Control group (n=8) was administered only vehicle and enzyme activities were measured. Serum AST:ALT ratios were also computed for all the groups. Results: Theobromine administration in moderate (600 mglkg body weight) to high (700 mglkg body weight) doses induced a highly significant (p<0.001) time and dose dependent increase in aspartate aminotransferase (AST) activities of the serum and heart tissue, but not of the liver. Similarly, the alanine aminotransferase activities of theobromine treated animals were significantly higher (p<0.001) for the heart, and (p<0.05) for the serum compared with their respective controls at 700 mglkg body weight. There were no changes in the ALT activities in the liver tissue. The computed AST:ALT ratio for the theobromine treatment group showed an increase with values of 1.93 and 2.01 for the 600mg/kg and 700 mg/kg theobromine dose regimens respectively, compared with the control value of 1.37. Conclusion: Theobromine toxicity appears to be heart directed.