Central effects of Ro 19-6327 given acutely and repeatedly.
Some central effects of Ro 19-6327--a new MAO-B inhibitor--were studied in mice and rats. Given in low doses (1 or 3 mg/kg) Ro 19-6327 did not affect the locomotor activity of mice but its high dose (10 mg/kg) increased the activity. In rats Ro 19-6327 inhibited the locomotor activity but the effect was not dose dependent and not always significant. Ro 19-6327 did not change the locomotor activity in mice induced by L-DOPA (plus benserazide--an inhibitor of peripheral decarboxylase). The drug suppressed the reserpine-induced hypothermia and ptosis in mice and partly counteracted the apomorphine-induced hypothermia. It markedly enhanced (10 mg/kg) the amphetamine-induced stereotypy in rats. L-5-Hydroxytryptophan (L-5-HTP)-induced head twitch response was unchanged by Ro 19-6327. The drug given three times was inactive in forced swimming test. Repeated treatment with Ro 19-6327 (twice daily for 14 days) produced the enhancement of (+)-amphetamine- and nomifensine-induced hyperactivity in rats. Unlike a number of antidepressants, Ro 19-6327 did not potentiate the clonidine aggressiveness in mice, but--in contrast--inhibited it. The results suggest that Ro 19-6327 given repeatedly produces no changes in the responsiveness of the alpha-adrenergic system (in references to effects mediated by alpha 1-adrenoceptors). Adaptive changes in dopamine system are doubtful.
Skuza
G
G
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
Rogóz
Z
Z
D000818:Animals; D004334:Drug Administration Schedule; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D010848:Picolinic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D011942:Receptors, Adrenergic, alpha; C059303:lazabemide; D007980:Levodopa