ABSTRACT
meta-Chlorophenylpiperazine (mCPP) is a compound that is frequently used in challenge tests of the serotonergic system. Its human pharmacology is largely unexplored. The objective of this study was to investigate the pharmacokinetic and pharmacodynamic profile of mCPP. Eight female and six male healthy volunteers were included in a randomized, double-blind, double-dummy, three-way crossover design of single-dose intravenous (0.1 mg/kg), oral (0.5 mg/kg), and placebo treatment, with 24-hour follow-up. mCPP showed a large variability in clearance (11-92 mL/hr) and bioavailability (14-108%). Two female subjects dropped out because of headache and dysphoria. During the 27 occasions in which mCPP was administered, autonomic physical symptoms were observed in 23 subjects and disturbances of mood in 6 subjects. Oral and intravenous mCPP caused sudden increases in cortisol levels, prolactin levels, and total scores of the Body Sensation Questionnaire. Administration of mCPP also led to concentration-dependent increases of saccadic peak velocity and adaptive tracking performance and to a decrease of electroencephalographic occipital theta activity. No clinically relevant effects on electrocardiogram, temperature, and blood pressure were found. In conclusion, it is doubtful whether mCPP is a useful compound for challenge tests in view of the large pharmacokinetic variability after intravenous and oral administration. The effects of mCPP are consistent with disinhibition of the central nervous system.
Subject(s)
Piperazines/pharmacokinetics , Serotonin Receptor Agonists/pharmacokinetics , Administration, Oral , Adult , Arousal/drug effects , Central Nervous System/drug effects , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Metabolic Clearance Rate/physiology , Neural Inhibition/drug effects , Piperazines/pharmacology , Serotonin Receptor Agonists/pharmacologyABSTRACT
In a previous study performed in south Sulawesi (Sulawesi Selatan), Indonesia, we established that the immunoglobulin G4 (IgG4) enzyme-linked immunosorbent assay (ELISA) is a suitable community diagnostic method and that it can distinguish areas of high and low prevalences within short distances. In an attempt to make this diagnostic tool more applicable in the field, a comparative study using serum and blood collected on filter paper was undertaken with 568 individuals living in 2 areas with different endemicity for brugian filariasis in south Sulawesi. In Mamuju district, where the microfilaria (mf) prevalence of the studied individuals was 18.4%, antifilarial IgG4 was present in 73.1% of the venepuncture samples and 72.5% of the filter paper samples, respectively. In Mangkutane district, where lymphatic filariasis is transmitted at a low level (mf rate 2.4%), antifilarial IgG4 was detected in 35.5% and 39.9% of similar samples, respectively. There was no significant difference in the IgG4 detection rate determined from venepuncture and filter paper samples from the same donors (P = 0.124), and the IgG4 values were highly correlated (p = 0.97, P < 0.001, n = 568). These results indicate that the filter paper technique for collection of blood samples is a suitable alternative to venepuncture for use in the IgG4 ELISA.
