The pharmacological properties of
MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]
pyridine maleate) as an
antidepressant were investigated. At doses 10 times less than those of
amitriptyline,
MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by
L-DOPA. Intermediate doses of
MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized
clonidine-induced suppression of exploratory activity in mice.
MO-8282 moderately antagonized the ptosis but not the
hypothermia induced by
reserpine in mice.
MO-8282 exhibited weak antagonism against the
tremor, lacrimation and
diarrhea induced by
tremorine, but its activity was milder than that of
amitriptyline. The uptake of
noradrenaline into rat hypothalamic synaptosomes was inhibited by
MO-8282 at concentrations 20 times less than equally effective doses of
amitriptyline, but the uptake of
dopamine or
serotonin was unaffected by
MO-8282. A single
oral administration of
MO-8282 at a dose of 30 mg/kg accelerated
noradrenaline turnover, but did not affect
dopamine and
serotonin turnover in the rat brain.
MO-8282 strongly inhibited
noradrenaline-,
histamine- or
adenosine-sensitive
adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of
imipramine, rather resembling that of
mianserin.
MO-8282 did not affect
monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of
MO-8282 are different from those of
tricyclic antidepressants and rather similar to those of
mianserin, but more potent. The results, therefore, indicate that
MO-8282 is possibly a novel
antidepressant.