The attenuating effect of carteolol hydrochloride, a β-adrenoceptor antagonist, on neuroleptic-induced catalepsy in rats

It is known that β-adrenoceptor antagonists are effective in the treatment of akathisia, one of the extrapyramidal side effects that occur during neuroleptic treatment. Neuroleptic-induced catalepsy, a model of neuroleptic-induced extrapyramidal side effects, was considered suitable as a model for predicting neuroleptic-induced akathisia in humans, although neuroleptic-induced catalepsy was not considered a specific test for neuroleptic-induced akathisia. Therefore, the effects of carteolol, a β-adrenoceptor antagonist, on haloperidol-induced catalepsy in rats were behaviorally studied and compared with those of propranolol and biperiden, a muscarinic receptor antagonist. Carteolol, as well as propranolol and biperiden, inhibited the haloperidol-induced catalepsy. The inhibitory effect of carteolol was almost comparable to that of propranolol, but was weaker than that of biperiden. Carteolol did not evoke postsynaptic dopamine receptor-stimulating behavioral signs such as stereotypy and hyperlocomotion in rats. Carteolol did not antagonize the inhibitory effects of haloperidol on apomorphine-induced stereotypy and locomotor activity in rats. In addition, carteolol did not evoke 5-HT1A receptor-stimulating behavioral signs such as flat body posture and forepaw treading and did not inhibit 5-hydroxytryptophan-induced head twitch in rats. Finally, carteolol did not inhibit physostigmine-induced lethality in rats. These results strongly suggest that carteolol improves haloperidol-induced catalepsy via its β-adrenoceptor antagonistic activity and is expected to be effective in the treatment of akathisia without attenuating neuroleptic-induced antipsychotic effects due to its postsynaptic dopamine receptor antagonistic activity.