Effect of chronic administration of the 6-aza analogue of mianserin (Org. 3770) and its enantiomers on behaviour and changes in noradrenaline metabolism of olfactory-bulbectomized rats in the “open field” apparatus

Abstract

Following its chronic administration, the racemic mianserin analogue of Org. 3770 attenuated the hypermotility of bilaterally olfactory-bulbectomized rats in the “open-field” apparatus, over the dose range of 0.5–2 mg/kg; only the largest dose of the drug was found to reduce the motility of the sham-operated animals. The activity of this compound would appear to reside in its S(+)isomer; the R(−)isomer being inactive. Bulbectomy was associated with a slight decrease in the concentration of noradrenaline and its major metabolite MHPG in the amygdaloid cortex and mid-brain. Following chronic administration of Org. 3770, the concentration of noradrenaline and MHPG returned to control levels. When the enantiomers were tested, it was found that the behaviourally-inactive R(−)isomer was most effective in normalizing the deficit in this neurotransmitter. Thus, no correlation could be found between the behavioural activity of the enantiomers of Org. 3770 and changes in the metabolism of noradrenaline in the amygdaloid cortex and mid-brain.