Pharmacokinetic evaluation of eltoprazine

Abstract

Although clinical studies of eltoprazine did not conclusively demonstrate its efficacy in treating pathological aggression in humans, eltoprazine has shown to be a well-tolerated drug in both healthy volunteers and patients across several indications studied thus far. More recently, the role of eltoprazine in reducing symptoms of ADHD in adults has been explored in a clinical trial. Future research may provide endophenotypical characteristics to help identify specific subgroups of patients with ADHD, who can benefit from the development of eltoprazine, to maximize efficacy while minimizing adverse reactions.

Eltoprazine counteracts l-DOPA-induced dyskinesias in Parkinson’s disease: a dose-finding study

“…Doses ranging between 0.25 and 30 mg have been administered to healthy subjects or patients in the aforementioned clinical trials. The doses (2.5, 5 and 7.5 mg) administered in this study were lower than those given to most of the healthy volunteers (Raghoebar et al , 1990; Wigal and Duong, 2011) and patients in other populations (Verhoeven et al , 1992; Kohen et al , 1993; Tiihonen et al , 1993; de Koning et al , 1994; ClinicalTrials.gov Identifier: NCT01266174). It was therefore believed that the benefit that could be obtained from this study would outweigh any risks.…”

“…Dose selection for this trial was based on previous clinical experience with eltoprazine demonstrating ‘neuroactivity’ (Raghoebar et al , 1990; Verhoeven et al , 1992; Kohen et al , 1993; Tiihonen et al , 1993; de Koning et al , 1994; Wigal and Duong, 2011; ClinicalTrials.gov Identifier: NCT01266174) as well as conventional scaling calculations based on pharmacokinetic exposures in various animal model studies demonstrating neuroactivity. Doses ranging between 0.25 and 30 mg have been administered to healthy subjects or patients in the aforementioned clinical trials.…”

“…Oral or intravenous eltoprazine has previously been administered to >600 male and female subjects in single and multiple dose safety and efficacy studies (Raghoebar et al , 1990; Verhoeven et al , 1992; Kohen, 1993; Tiihonen et al , 1993; de Koning et al , 1994; Wigal and Doung, 2011). Doses, ranging between 0.25 and 30 mg, were given to ∼300 healthy subjects (Raghoebar et al , 1990; Wigal and Duong, 2011) and >300 patients suffering from mental handicap and aggression (Verhoeven et al , 1992; Kohen et al , 1993; Tiihonen et al , 1993; de Koning et al , 1994) or attention deficit hyperactivity disorder (ADHD; ClinicalTrials.gov Identifier: NCT01266174).…”

“…Doses, ranging between 0.25 and 30 mg, were given to ∼300 healthy subjects (Raghoebar et al , 1990; Wigal and Duong, 2011) and >300 patients suffering from mental handicap and aggression (Verhoeven et al , 1992; Kohen et al , 1993; Tiihonen et al , 1993; de Koning et al , 1994) or attention deficit hyperactivity disorder (ADHD; ClinicalTrials.gov Identifier: NCT01266174). Overall the drug has been safe and well-tolerated.…”

Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia

“…Eltoprazine (originally DU-28853) is a strong 5-HT1A/B receptor agonist initially developed for the treatment of pathological aggression in intellectually disabled patients. 118 The antidyskinetic properties of this molecule are due to 5-HT1A-and 5-HT1B-mediated inhibition of serotonin neurons responsible for the uncontrolled stimulation of supersensitized dopamine D1 receptors, which is characteristic of LID state. Acute administration of eltoprazine reduced LID in 6-OHDA lesioned rats and in MPTP monkeys treated with L-dopa.…”