title: Further pharmacological characterization of eltoprazine: focus on its anxiolytic, anorexic, and adverse‑effect potential.
abstract: Eltoprazine, a drug that had previously been developed for aggression, has recently been investigated for L-DOPA-induced dyskinesia in animal models of Parkinson´s disease (PD) and in dyskinetic PD patients. Much less is known about effects of eltoprazine in other therapeutic indications. Indeed, the pharmacological profile of eltoprazine might suggest its effects on anxiety and food intake, but also adverse effect potential, which is the focus of the present study. Given for 2 weeks either as infusion or as twice-daily treatment, eltoprazine produced a decrease in food intake and body weight at doses leading to 200-500 nM plasma concentrations. In the elevated plus maze eltoprazine increased anxiety‑like behavior. On the other hand, it induced a clear‑cut anxiolytic effect in context fear conditioning test starting at ca. 0.3 mg/kg, and failed to produce any significant effect in fear potentiated startle test. Regarding adverse effects, eltoprazine was found to produce hypothermia starting from 1 mg/kg. At s imilar doses it also increased locomotion in the open field. However, eltoprazine failed to affect acquisition in context fear conditioning paradigm, which may indicate lack of its detrimental effect on learning at the doses tested (i.e., up to 5 mg/kg). In summary, effects of eltoprazine in different anxiety tests were equivocal while its effect on body weight seems robust and requires further investigation. It is to be determined whether these effects can be expected at the doses free of adverse effects.
authors.affiliation: Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gravius
authors.affiliation: Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Dekundy
authors.affiliation: Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Vanaga
authors.affiliation: Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Franke
authors.affiliation: Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany, wojciech.danysz@merz.de.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Danysz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001007:Anxiety / Q000097:blood / Q000188:drug therapy*; D001067:Appetite Depressants / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014151:Anti-Anxiety Agents; D001067:Appetite Depressants; D010879:Piperazines; C063828:eltoprazine