The pharmacological properties of AD-5423 [2-(4-ethyl-1-piper-azinyl)-4- (4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine] were studied in biochemical and behavioral tests. In vitro, AD-5423 bound preferentially to dopamine (DA)-D2 (Ki, 14.8 nM; cf. haloperidol, 8.79 nM; and clozapine, 149 nM) and serotonin (5-HT)-S2 (Ki, 3.98 nM; cf. haloperidol, 26.8 nM; and clozapine, 8.66 nM) receptors. It displayed low affinity for adrenaline (Ad)-alpha-1 (Ki, 56.3 nM) receptors and was virtually devoid of binding to DA-D1 (Ki, 2870 nM), 5-HT-S3, Ad-alpha-2, Ad-beta, muscarine, tau-aminobutyric acid and benzodiazepine receptors. In addition, AD-5423 was only a weak inhibitor of DA, 5-HT and noradrenaline uptake systems. When administered p.o., AD-5423 (0.3-10 mg/kg) increased brain contents of the DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in mice and rats and the 5-HT metabolite 5-hydroxyindoleacetic acid in mice. Behaviorally, AD-5423 (0.2-2 mg/kg p.o.) decreased exploratory activity in mice, suppressed conditioned avoidance responding and methamphetamine-induced hyperactivity in mice and rats, antagonized apomorphine-induced gnawing in rats and vomiting in dogs and reduced hostile responses in monkeys. In these effects, AD-5423 was more or less equi-potent to haloperidol. However, AD-5423 (10 mg/kg p.o.), unlike haloperidol, did not antagonize SKF38393-induced vacuous oral movements in rats. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane in mice and by para-chloroamphetamine in rats were antagonized by AD-5423 at much lower doses (0.5-2 mg/kg p.o.) than those of haloperidol and clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)