In vivo effect of RU 24722 and drugs used for the treatment on senile cerebral insufficiency on rat brain ornithine decarboxylase.
RU 24722, a compound selected for its protective effect against cerebral anoxia and ischemia in rats, induced a dose-dependent increase in brain ornithine decarboxylase (ODC), a rate limiting enzyme in the biosynthesis of polyamines. This action already 2 hr after injection, increased at 4 and 6 hr and ODC activity returned to pretreatment levels at 16 hr. Since it has been shown previously that glucocorticoids stimulate brain ODC, it was considered necessary to know if corticosterone could play a role in the action of RU 24722. This compound increased serum corticosterone levels 1 hr after injection, its effect being nil at 4 hr. Nevertheless, the effect of RU 24722 on brain ODC does not appear to be entirely dependent on the increase of serum corticosterone. the delays needed to obtain a stimulation of the enzyme by the steroid are longer (6 hr) than those necessary to observe the action of the drug (2 hr)on brain ODC. Furthermore, RU 24722 increased brain ODC even in adrenalectomized animals. In order to get an insight on the interaction of RU 24722 with putative transmitters, we have studied the effect of the compound on brain ODC in the presence of different pharmacological agents. Experiments performed using noradrenergic agonists and antagonits suggest that the action of RU 24722 on brain ODC is due to the blockade of inhibitory post-synaptic alpha-2 adrenoceptors. We have studied the action of other compounds, used for the treatment of senile cerebral insufficiency: codergocrine, dihydroergocristine, dihydroergocryptine, dihydroergocornine, dihydroergocristine and piribedil increased rat brain ODC; vincamine, piracetam and nicergoline were devoid of any action.
D000315:Adrenalectomy; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy*; D003000:Clonidine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004347:Drug Interactions; D004879:Ergotamines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*; D014749:Vincamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D004879:Ergotamines; D014665:Vasodilator Agents; D014748:Vinca Alkaloids; D015016:Yohimbine; D001285:Atropine; D014749:Vincamine; D011433:Propranolol; C044616:vindeburnol; D009955:Ornithine Decarboxylase; D006220:Haloperidol; D003000:Clonidine; D003345:Corticosterone; D010646:Phentolamine