Central effects of Ro 19-6327 given acutely and repeatedly

Pol J Pharmacol Pharm. Nov-Dec 1991;43(6):437-47.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Administration Schedule
  • Levodopa / pharmacology
  • Male
  • Mice
  • Monoamine Oxidase Inhibitors / administration & dosage
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Motor Activity / drug effects
  • Picolinic Acids / administration & dosage
  • Picolinic Acids / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, alpha / drug effects*

Substances

  • Monoamine Oxidase Inhibitors
  • Picolinic Acids
  • Receptors, Adrenergic, alpha
  • lazabemide
  • Levodopa