7 and 8 Two Way ANOVA followed by Bonferroni
post hoc multiple comparison test was performed to find the significance of pharmacodynamic studies. Statistical analysis was performed via Prism software (v. 5.0; GraphPad Software, Inc., San Diego, CA). Pharmacokinetic profile was obtained from three animals in each cohort. Using the pooled estimate of the total variance, the 95% confidence intervals were regarded as being statistically confirmed and shown in find more Table 1. At 0 h, all the animals were observed for spontaneous behaviour of ipsilateral paw. The spontaneous behaviour of the ipsilateral paw was significantly observed compared to contralateral paw. Following treatment of LMT, spontaneous behaviour, threshold pressure, cold allodynic effect has been significantly altered at 2 h (P < 0.001) and maximum percent reversal of pain was found to be at 2 h (P < 0.001) post dose. From the plasma concentration profile of the LMT, Cmax was found out to be 4.23 ± 0.63 μg/ml at 2 h, the pharmacodynamic data also showed a significant raise in paw withdrawal duration on spontaneous pain and paw withdrawal threshold on hyperalgesia at Cmax due to higher correlation coefficient with R2 > 0.9 from Fig. 2 between the concentration of drug and the % pain
reversal on mechanical hyperalgesia and spontaneous pain. Hence, it is clearly evident that there was a positive ISRIB molecular weight below correlation. Further, the results of correlation (Table 1) proved that the pharmacokinetics of the drug are in greater correlation with the pharmacodynamic action. The data for Lamotrigine revealed that the maximum drug concentration obtained was found to be similar to that demonstrated by Jochen.9 From early trial phase
3 studies performed by Peck,10 the therapeutic anticonvulsant serum concentration was between 1 and 4 μg/ml and 3–14 μg/ml has proven to be quite safe. The extent of bioavailability (AUC0–24) was similar to the range reported by Jochen to be 69.75 μg/ml. The single dose of the drug was found to be sufficient to show the therapeutic efficacy as previously described by Jacques.11 From our findings, there was a significant effect on spontaneous pain and mechanical hyperalgesia by acting as a sodium channel blocker and an inhibitor for glutamate release. The present study, failed to produce significant anti-allodynic effects which can be comparable to the result obtained12 which did not result in overt behavioural side effects. Most preclinical and clinical studies assess antinociceptive activity on neuropathic pain by drug efficacy on a dose-effect basis (i.e. reduction of pain).