S 14506 (1-[-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl)piper azine hydrochloride),
8-OH-DPAT ((+/-)-8-hydroxydipropylaminotetralin hydrobromide),
clozapine and
raclopride were compared in some behavioural models able to characterize
dopamine antagonist properties. In mice treated with
apomorphine (0.75 mg/kg, s.c.), stereotyped climbing and sniffing were dose dependently antagonized by
S 14506, by
clozapine and by
raclopride, but were virtually not modified by
8-OH-DPAT. Stereotyped climbing and sniffing induced by (+)-
amphetamine (1.25 mg/kg, s.c.) in mice treated with
L-DOPA (
L-3,4-dihydroxyphenylalanine 75 mg/kg, associated with
benserazide, i.p.) were also dose dependently antagonized by
S 14506 and by
raclopride, but were only partially antagonized by
clozapine and unaffected by
8-OH-DPAT. Grooming behaviour induced by
SK&F 38393 ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride, 1.87 mg/kg, s.c.) in mice was inhibited by low doses of
S 14506 and of
clozapine, and by relatively high doses of
8-OH-DPAT and of
raclopride. The decreased grooming behaviour observed in
apomorphine-treated mice was partly antagonized by high dose of
raclopride but was significantly potentiated by
S 14506,
8-OH-DPAT and
clozapine.
Raclopride produced the same effect in mice treated with (+)-
amphetamine and
L-DOPA. In rats treated with
apomorphine (0.6 mg/kg, s.c.), sniffing was dose dependently antagonized by
S 14506, by
raclopride and by
clozapine, but not by
8-OH-DPAT. Again, whereas increasing doses of
raclopride allowed grooming to reappear in
apomorphine (0.6 mg/kg)-treated rats,
S 14506,
8-OH-DPAT and
clozapine did not.
Raclopride induced
catalepsy in rats, whereas like
clozapine,
S 14506 was virtually ineffective. All the tested compounds inhibited in vitro [3H]
raclopride binding in rat striatum (
raclopride >
S 14506 >
clozapine > 8-
OH-DPAT), whereas only
clozapine inhibited [3H]
SCH 23390 binding. Finally,
S 14506 inhibited the in vivo binding of [3H]
raclopride in striatum and olfactory bulbs, but did not affect the striatal in vivo binding of [3H]
SCH 23390. From these data, it appears that like
raclopride,
S 14506 displays
dopamine antagonist properties by blocking
dopamine D2 receptors. However, the psychopharmacological profile of
S 14506 is closer to that of
clozapine than to that of
raclopride, probably as a result of its actions at
5-HT receptors.