Study of the participation of the dopaminergic transmission system in the effects of two newly synthesized barbiturates.
The effects of two newly synthesized barbiturates--HB-7 (2-hydroxylamino-5-ethyl-5-sec. pentylbarbituric acid) and HB-2 (2-hydroxylamino-5-ethyl-5-propylbarbituric acid--on models of apomorphine stereotypy and haloperidol catalepsy were investigated in experiments on male rats and mice. The test drugs used were phenobarbital (PB)--in stereotypy and catalepsy, and diphenylhydantoin (DPH)--in catalepsy. HB-7 changes the stereotypy considerably: it developed faster and disappeared faster than in the control group. Phenobarbital had a weaker effect on the intensity and duration of the stereotypy. Catalepsy was induced with haloperidol in doses of 1 and 2 mg/kg. HB-7 and HB-2 weakened haloperidol catalepsy, compared with PB and DPH. The faster occurrence of apomorphine stereotypy and the weakening of the haloperidol-induced catalepsy under the effect of the two hydroxyl-amine derivatives of barbituric acid suggest an effect on the cerebral dopaminergic transmission. This effect may be mediated through the effect of HB-7 on DA-ergic transmission or through the GABA-ergic transmission in the brain structures responsible for these behavioural reactions.
Getova
D
D
Experimental Pharmacology Department, Bulgarian Academy of Sciences.
Markovska
V
V
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001463:Barbiturates / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000031:analogs & derivatives* / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D001463:Barbiturates; D011954:Receptors, Dopamine; C056510:2-hydroxylamine-5-ethyl-5-sec-pentylbarbituric acid; C058539:2-hydroxylamino-5-ethyl-5-propylbarbituric acid; D010672:Phenytoin; D010424:Pentobarbital; D006220:Haloperidol; D001058:Apomorphine