Mirtazapine enhances the effect of haloperidol on apomorphine-induced climbing behaviour in mice and attenuates haloperidol-induced catalepsy in rats.
Activation of 5-HT1A receptors has been shown to attenuate catalepsy induced by typical antipsychotic compounds. Since mirtazapine (Remeron; Org 3770) has indirect 5-HT1A receptor stimulating properties as well as antagonist properties at alpha2-adrenoceptors and 5-HT2 receptors, it was of interest to investigate how the compound could modulate the effect of haloperidol on apomorphine-induced climbing behaviour in mice and haloperidol-induced catalepsy in rats. In the apomorphine climbing test, it was found that mirtazapine (2.2-22 mg/kg) did not change the climbing behaviour of mice induced by 1 mg/kg of apomorphine. However, when given as a co-treatment with haloperidol, mirtazapine (1 and 10 mg/kg) dose-dependently augmented the inhibiting effect of haloperidol on this climbing behaviour. Co-treatment with the 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) also augmented the effect of haloperidol. Catalepsy induced by haloperidol (4.6 mg/kg) was attenuated by mirtazapine (2.2-22 mg/kg). The strongest effect was seen at 90 min after haloperidol treatment. The results obtained in these experiments suggest that co-treatment with mirtazapine may enhance the antipsychotic effect of haloperidol and reduce its extrapyramidal side effects, thereby widening its therapeutic window.
Berendsen
H H
HH
Department of Neuropharmacology, N.V. Organon, Oss, The Netherlands. h.berendsen@organon.oss.akzonobel.nl
Broekkamp
C L
CL
Pinder
R M
RM
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000523:psychology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D000078785:Mirtazapine; D051381:Rats; D017207:Rats, Sprague-Dawley
D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D008803:Mianserin; D000078785:Mirtazapine; D006220:Haloperidol; D001058:Apomorphine