The invention concerns substituted tricyclic isoxazoline derivatives, more
in particular tricyclic dihydrobenzopyranoisoxazoline,
dihydroquinolinoisoxazoline, dihydronaphthalenoisoxazoline and
dihydrobenzothiopyranoisoxazoline derivatives substituted on at least one
of the C6- and C9-positions of the phenylpart of the tricyclic moiety
with a selected radical, according to Formula (I) ##STR00001## wherein
X=CH.sub.2, N--R.sup.7, S or O, R.sup.1, R.sup.2, R.sup.14 and R.sup.15
are certain specific substituents, with the proviso that at least one of
R.sup.14 and R.sup.15 is not hydrogen, Pir is preferably an optionally
substituted piperidinyl or piperazinyl radical and R.sup.3 represents an
optionally substituted aromatic homocyclic or heterocyclic ring system
including a partially or completely hydrogenated hydrocarbon chain of
maximum 6 atoms long with which the ring system is attached to the Pir
radical and which may contain one or more heteroatoms selected from the
group of O, N and S; a process for their preparation, pharmaceutical
compositions comprising them and their use as a medicine, in particular
for the treatment of depression, anxiety, movement disorders, psychosis,
Parkinson's disease and body weight disorders. The compounds according to
the invention have surprisingly been shown to have a serotonine (5-HT)
reuptake inhibitor activity in combination with additional
.alpha..sub.2-adrenoceptor antagonist activity and show a strong
anti-depressant activity without being sedative. The invention also
relates to novel combination of isoxazoline derivatives according to the
invention with one or more other compounds selected from the group of
antidepressants, anxiolytics, anti-psychotics and anti-Parkinson's
disease drugs to improve efficacy and/or onset of action.