Ginkgo biloba leaf extract (EGb 761) enhances catalepsy induced by haloperidol and L-nitroarginine in mice

Ginkgo biloba extract EGb 761 has been reported to have therapeutic effects which have been attributed to anti-oxidant and free radical-scavenging activities, including a direct action on nitric oxide production. L G-nitro-arginine (L-NOARG), a nitric oxide synthase inhibitor, and haloperidol, a drug that blocks dopamine receptors, are both known to induce catalepsy in rodents. Nitric oxide has been shown to influence dopaminergic transmission in the striatum. The purpose of the present study was to evaluate the effect of the extract obtained from leaves of Ginkgo biloba tree EGb 761 on catalepsy induced by haloperidol or by L-NOARG. Albino Swiss mice (35-45 g, N = 8-12) received by gavage a single or repeated oral dose (twice a day for 4 days) of EGb 761 followed by ip injection of haloperidol or L-NOARG. After the treatments, the animals were submitted to behavioral evaluation using the catalepsy test. Acute treatment with 80 mg/kg EGb did not modify the catalepsy induced by L-NOARG but, the dose of 40 mg/kg significantly enhanced haloperidol-induced catalepsy measured at the 10th min of the test. After repeated treatment with 80 mg/kg EGb 761, a significant increase in the cataleptic effect produced by both haloperidol and L-NOARG was observed. These data show that repeated EGb 761 administration increases the effects of drugs that modify motor behavior in mice. Since the catalepsy test has predictive value regarding extrapyramidal effects, the possibility of pharmacological interactions between haloperidol and Ginkgo biloba extracts should be further investigated in clinical studies.

Stereoselectivity of the anxiolytic effect of propranolol microinjected into the dorsal midbrain central gray

In a previous study we have shown that microinjection of d,I-propranolol into the dorsal midbrain central gray of the rat causes an anxiolytic effect in the elevated plus-maze model which is lilkely to be mediated by endogenous 5-hydroxytryptamine. In the present experiment, the effects of 1- and d,1-propranolol were compared under the same experimental conditions. Both the I-isomer and the racemic mixture increased the percentage of open arm entries without affecting the total number of entries into either open or enclosed arms of the maze, thus reproducing the selective anxiolytic effect previously described. The doses of 5 nmol 1-propanolol and 10 nmol d,1-propranolol caused anxiolytic effects of comparable magnitude, while the doses of 2,5 nmol of the former and 5 nmol of the latter were ineffective. Therefore, the 1-isomer was nearly twice as potent as the racemic mixture, thus being responsible for the pharmacological activity observed. These results are compatible with the proposal that propranol blocks stereospecific autoreceptors in serotonergic nerve endings that inhibit neurotransmitter release