Biomedical subjects

M Aravagiri

Publications and source records attributed to M Aravagiri.

39 records · Page 3Linked to original sources

PubMed1984

Radioimmunoassay for the sulfoxide metabolite of trifluoperazine and its application to a kinetic study in humans.

Antibodies were produced in rabbits immunized with 10-[[3-[4-(2-carboxyethyl)-1-piperazinyl]-propyl]]-2 -trifluoromethyl-10H-phenothiazine sulfoxide-bovine serum albumin conjugate. The subsequently developed radioimmunoassay (RIA) procedure enables, for the first time, the quantitation of the sulfoxide metabolite of trifluoperazine in the plasma of humans after administration of therapeutic doses of trifluoperazine, in which 60 pg of the sulfoxide metabolite in 200 microL of plasma can be measured with a CV of less than 3%. Similar results were obtained by this assay with or without a benzene extraction step and also in the presence or absence of a large excess of trifluoperazine and suspected major metabolites of trifluoperazine. This RIA procedure, together with a previously developed RIA for trifluoperazine was used to directly determine plasma concentrations of trifluoperazine and its sulfoxide metabolite after administration of a single, low, oral dose of trifluoperazine to five healthy volunteers. The rapidly appearing, relatively high concentrations of the sulfoxide metabolite are indicative of presystemic sulfoxidation. The mean plasma elimination half-life for the sulfoxide metabolic of trifluoperazine was 5.8 +/- 1.3 h.

Humans↗

PubMed1983

Radioimmunoassays for phenothiazine drugs and their major metabolites in plasma.

Radioimmunoassay procedures have been developed for some phenothiazine drugs and their major metabolites which are capable of quantitating 0.3 ng/ml or less in a 200 microliter plasma sample with a coefficient of variation less than 3%. They were developed with a view to their use in pilot investigations of plasma level versus clinical response correlations. The development of the procedures for trifluoperazine are described in this workshop. Antisera to trifluoperazine have been raised in New Zealand white rabbits to several different types of immunogens, where there was variation in the length and nature of the N-10 side chain attached to the phenothiazine nucleus, as well as in the number of hapten residues coupled to bovine serum albumin. An improved radioimmunoassay for trifluoperazine has been developed which showed cross-reactivities to the N-desmethyl and 7-hydroxy metabolites of trifluoperazine of the order of 12 and 11%, respectively, in comparison to the 26 and 24% cross-reactivity, respectively, for the same metabolites by a previously reported procedure.

Antipsychotic Agents↗

PubMedDate not supplied

Regional differences in chronic neuroleptic effects on extracellular dopamine activity.

The extracellular levels of dopamine (DA) and DA metabolites in the caudate-putamen (CPu) and the nucleus accumbens (NA) of rats following administration of haloperidol (HAL) decanoate and fluphenazine (FLU) decanoate for 8 months were assessed using intracranial microdialysis 1 month after final injection. Both HAL- and FLU-treated animals showed persisting plasma neuroleptic levels at time of sacrifice. Extracellular basal levels of homovanillic acid (HVA) in the CPu were significantly elevated in the FLU-treated animals, while basal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the CPu were significantly elevated in the HAL-treated animals. Basal levels of DA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5HIAA) in the CPu were not significantly different between groups. No significant between-group differences were found for basal levels of any of the analytes in the NA. Neuroleptic-treated animals showed an enhanced response to direct infusion through the dialysis probe of amphetamine (1 microM) and nomifensine (10 microM) in the CPu but not the NA. These results suggest that chronic neuroleptic treatment produces enhanced extracellular DA activity in nigrostriatal, but not mesolimbic DA pathways.

3,4-Dihydroxyphenylacetic Acid↗