Psychomotor and cognitive effects of a single oral dose of talnetant (SB223412) in healthy volunteers compared with placebo or haloperidol.

Abstract

Central Nervous System (CNS) effects of talnetant, an NK-3 antagonist in development for schizophrenia, were compared to those of haloperidol and placebo. The study was randomised, double-blind, three-way crossover of talnetant 200 mg, haloperidol 3 mg or placebo. Twelve healthy males participated and EEG, saccadic and smooth pursuit eye movements, adaptive tracking, body sway, finger tapping, hormones, visual analogue scales (VAS) for alertness, mood and calmness and psychedelic effects, left/right distraction task, Tower of London and Visual and Verbal Learning Task were assessed. Haloperidol showed (difference to placebo; 95% CI; p-value) decreases in EEG alpha power (-0.87microV; -1.51/-0.22; p = 0.0110), saccadic inaccuracy (2.0%; 0.5/3.6; p = 0.0133), smooth pursuit eye movements (-7.5%; -12.0/-3.0; p = 0.0026), adaptive tracking (-3.5%; -5.4/-1.7; p = 0.0009), alertness (-6.8 mm; -11.1/-2.4; p = 0.0039), negative mood (-4.6 mm; -8.6/-0.6; p = 0.0266), the ability to control thoughts (1.2 mm; 0.2/2.3; p = 0.0214), and an increase of serum prolactin (ratio 4.1; 3.0/5.6; p < 0.0001). Talnetant showed decreased alpha power (-0.69 muV; -1.34/-0.04; p = 0.0390), improved adaptive tracking (1.9%; 0.1/3.7; p = 0.0370) and reduced calmness on VAS Bond and Lader (-4.5 mm; -8.0/-1.0; p = 0.0151). Haloperidol effects were predominantly CNS-depressant, while those of talnetant were slightly stimulatory. The results suggest that talnetant penetrates the brain, but it remains to be established whether this dose is sufficient and whether the observed effect profile is class-specific for NK3-antagonists.

• Authors: M Liem-Moolenaar, F A Gray, S J de Visser, K L Franson, R C Schoemaker, J A J Schmitt, A F Cohen, J M A van Gerven
• Journal: Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 24 Issue 1 Pg. 73-82 (Jan 2010) ISSN: 1461-7285 [Electronic] United States
• PMID: 18755817 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Antipsychotic Agents
• Quinolines
• Receptors, Neurokinin-3
• SB 223412
• Haloperidol

Topics

• Adolescent
• Adult
• Aged
• Antipsychotic Agents (pharmacokinetics, pharmacology)
• Brain (drug effects, metabolism)
• Cognition (drug effects)
• Cross-Over Studies
• Double-Blind Method
• Female
• Haloperidol (pharmacology)
• Humans
• Male
• Middle Aged
• Psychomotor Performance (drug effects)
• Quinolines (pharmacokinetics, pharmacology)
• Receptors, Neurokinin-3 (antagonists & inhibitors)
• Young Adult