Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:60929-23-9 (Indeloxazine)
 17 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cerebral activating actions of indeloxazine HCl and its optical isomers were evaluated in comparison with those of several selective monoamine uptake inhibitors. The effects of indeloxazine and its optical isomers on monoamine uptake were also determined. Indeloxazine was equipotent to the (-)-isomer in desynchronizing the spontaneous electroencephalogram (EEG) in both mature and aged rats and in accelerating recovery of consciousness induced by concussive head trauma in mice, whereas the (+)-isomer showed about 3 times less potent activity than indeloxazine and the (-)-isomer. The potency of indeloxazine and the (-)-isomer in inhibiting [14C]norepinephrine (14C-NE) uptake was approximately 25-30 times more potent than that of the (+)-isomer. Maprotiline and viloxazine, selective NE uptake inhibitors, also showed facilitatory actions in concussed mice. Selective 5-hydroxytryptamine (5-HT) uptake inhibitors such as citalopram, alaproclate, and zimeldine showed little effect. Indeloxazine, the (-)-, and the (+)-isomers facilitated passive avoidance learning behavior with a bell-shaped response curve in normal rats. The potency of the (+)-isomer in inhibiting [14C]5-HT uptake was equipotent to those of both indeloxazine and the (-)-isomer. While citalopram, alaproclate, and zimeldine also facilitated the acquisition of learning behavior, maprotiline and viloxazine, as well as the dopamine uptake inhibitor amantadine, showed little influence on the latency of step-through behavior. Amitriptyline, with anticholinergic activity, impaired learning behavior. Indeloxazine, its optical isomers, citalopram, alaproclate, and zimeldine also ameliorated cycloheximide-induced disturbance of learning behavior in mice, while maprotiline and viloxazine showed little effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral activating properties of indeloxazine HCl and its optical isomers. 832 39

The potential antidepressant properties of indeloxazine hydrochloride were examined in vitro and in vivo. Indeloxazine showed preferential affinity for both [3H] citalopram (Ki: 22.1 nM) and [3H]nisoxetine binding sites (Ki: 18.9 nM) in membranes of the rat cerebral cortex. In microdialysis studies, intraperitoneal injection of indeloxazine (3 and 10 mg/kg) dose-dependently increased the extracellular level of both serotonin and norepinephrine in rat frontal cortex of freely moving rats. Amitriptyline was almost equivalent to indeloxazine in these two assays with the exception of a much weaker effect on extracellular serotonin levels. Spontaneous [3H]serotonin release from rat cortical synaptosomes was significantly enhanced by indeloxazine (10-1000 nM). In behavioral studies, indeloxazine increased the number of wheel rotations in forced swimming tests in both ICR mice (50 mg/kg, p.o.) and SAMP8//YAN, a substrain of senescence-accelerated mouse (20 and 30 mg/kg, p.o.). Indeloxazine (3-10 mg/kg p.o.) also inhibited the incidence of muricide in raphe-lesioned rats. These results suggest that indeloxazine is an inhibitor of serotonin and norepinephrine uptake and has potential antidepressant properties. In addition, the drug-induced enhancement of serotonin release may contribute to its potent effects on the serotonergic system in vivo.
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PMID:Neurochemical and behavioral characterization of potential antidepressant properties of indeloxazine hydrochloride. 983 47