Summary of the actions of S33138 compared to haloperidol, clozapine, olanzapine, and risperidone in models of potential antipsychotic properties compared to induction of extrapyramidal side effects
All antipsychotics were administered s.c. The first line gives the EC50 (CAR and APO), IC50 (A-LOC, C-LOC, P-LOC, and D-LOC), or minimal effective dose [catalepsy (CATAL) and prolactin (PRL)]. The second line shows the maximal observed effect (in percentage) followed by the maximally effective dose in brackets, with the exception of prolactin where maximal absolute levels are given in nanograms/milliliter. As can be deduced from the maximal effects, each drug (3-5 doses tested, n = 5-6 per dose) exerted highly significant effects in all models (P < 0.05 in ANOVA in every case), so F values are omitted for reasons of space. For cocaine (effect of S33138 not shown in Fig. 1), F(4,22) = 6.67, P < 0.01.
Drug | CAR | APO | A-LOC | C-LOC | P-LOC | D-LOC | CATAL | PRL |
|---|---|---|---|---|---|---|---|---|
| S33138 | 3.8 | 0.32 | 1.4 | 1.1 | 0.73 | 4.9 | 10.0 | 0.16 |
| 100 (20.0) | 100 (2.5) | 100 (10.0) | 100 (10.0) | 100 (10.0) | 86 (10.0) | 61 (40.0) | 75 (2.5) | |
| Haloperidol | 0.08* | 0.02 | 0.04 | 0.02 | 0.08 | 0.1 | 0.16 | 0.04 |
| 97 (0.63)* | 100 (0.16) | 100 (0.16) | 100 (0.16) | 100 (0.63) | 99 (0.63) | 100 (0.63) | 205 (0.63) | |
| Clozapine | 4.4* | 2.3 | 7.2 | 2.6 | 0.08 | 1.7 | >40.0 | 20.0 |
| 94 (20.0)* | 100 (5.0) | 100 (40.0) | 100 (40.0) | 100 (0.63) | 96 (10.0) | 2 (40.0) | 30 (20) | |
| Olanzapine | 0.60 | 0.08 | 0.30 | 1.6 | 0.002 | 0.44 | 5.0 | 0.63 |
| 90 (2.5) | 100 (0.63) | 100 (10.0) | 94 (10.0) | 100 (0.04) | 84 (2.5) | 81 (20.0) | 170 (10.0) | |
| Risperidone | 0.49 | 0.002 | 0.20 | 0.04 | 0.002 | 0.32 | 0.63 | 0.01 |
|
| 97 (2.5) | 100 (0.16) | 100 (2.5) | 100 (2.5) | 100 (0.04) | 100 (2.5) | 100 (5.0) | 83 (0.63) |
CAR, inhibition of conditioned avoidance responses in rat; APO, inhibition of climbing behavior elicited by apomorphine (0.75 mg/kg s.c.) in mice; LOC, inhibition of locomotion elicited in rats by amphetamine (A, 2.5 mg/kg i.p.), cocaine (C, 20.0 mg/kg i.p.), phencyclidine (P, 20.0 mg/kg s.c.), and dizocilpine (D, 0.16 mg/kg s.c.).
↵* Data from Millan et al., 1998.