Effects of tryptophan and valine administration on behavioral pharmacology of haloperidol

Development of antipsychotics with slight/no extra-pyramidal symptoms [EPS] and/or other side effects is one of the exploring fields of drug research. Haloperidol is a high potency typical neuroleptic used in the treatment of schizophrenia but produces muscles related side effects commonly known as EPS. These effects are not produced following the administration of atypical neuroleptics such as clozapine. A severe side effect of clozapine treatment is however, agranulocytosis. This involves investigation on the mechanism by which a typical neuroleptic acting via serotonergic mechanism tends to produce less or no EPS. The present study was, therefore, designed to determine the effect of serotonin precursor tryptophan and a large neutral amino acid other than tryptophan [valine] on the modulation of haloperidol induced catalepsy and akinesia. Cataleptic effects of the drug and activity reducing effects were monitored on inclined surface and in an activity box or open field respectively. The results are discussed in the context of a role of tryptophan and valine induced changes of brain serotonin in modifying the extrapyramidal and monoaminergic effects of the typical neuroleptic haloperidol. In the present study administration of TRP and valine decreased activity in rats, haloperidol-induced catalepsy' was not modulated by prior administration of tryptophan or valine. Brain serotonin levels were elevated by haloperidol treatment and correlated very well with the behavioral response. These findings suggest a possible serotonergic involvement in neuroleptic induced tardive dyskinesia and an amelioration of the disorder through TRP supplementation

Pharmacokinetic difference of some generic tablet gliclazide 80 mg on Pakistani population

The goal of rational drug therapy is to produce a desired pharmacological response in an acceptable and predictable manner while minimizing the occurrence of undesired events. The Pharmacokinetics of different generics of tablet gliclazide 80 mg was investigated on healthy [10 x 2], Pakistani subjects. For this exploration an open-label, randomized, two-period crossover [Balanced in Complete Block Design] study, was conducted The out come of the said study suggests that all generics were found analogous regarding pharmacokinetic behavior in-spite of having different excipients, concentration of excipients, sources of raw material, manufacturing process, machinery, resources and also inter individual variation of the study. Results of the study also undoubtedly advocate that generics manufactured in different manufacturing units of Pakistan are near to the standard formulation and produce comparable results. No significant differences in pharmacokinetics parameters were observed, however, minor differences might narrate with inter individual variation in human volunteers and in different generic as well as different pharmaceutical unit