ABSTRACT
We performed this study in order to verify the heart rate decrease caused by the D2-receptor on cardiac sympathetic nerve endings and its relation to the concentration of norepinephrine in synaptic clefts. Sprague-Dawley rats were pithed and the heart rate was increased either by electrical stimulation of the cardiac accelerator nerve or by intravenous infusion of norepinephrine, tyramine, or isoproterenol. Increased heart rate by electrical stimulation of cardiac accelerator nerve was dose-dependently lowered by lisuride and its effect was blocked by pretreatment with sulpiride but not with yohimbine and SCH 23390. Also, the heart rate was decreased in a dose-dependent manner by clonidine and this effect was blocked by pretreatment with yohimbine, but not with sulpiride. For increased heart rate by infusion of norepinephrine, tyramine, or isoproterenol, the heart rate lowering effect of lisuride was more marked in the norepinephrine-and tyramine-infusion groups, in which the intrasynaptic concentration of norepinephrine was elevated, compared to the isoproterenol-infusion group, in which intrasynaptic concentration of norepinephrine was not elevated. In conclusion, there is a D2-receptor on the cardiac sympathetic nerve endings which decreases the heart rate and is different from the presynaptic alpha 2-receptor. Also, the heart rate lowering effect via stimulation of the D2-receptor by lisuride was more marked with increased concentration of norepinephrine in the synaptic cleft.
Subject(s)
Female , Male , Rats , Animals , Heart/innervation , Heart Rate/drug effects , Lisuride/pharmacology , Norepinephrine/metabolism , Receptors, Dopamine D2/physiology , Sympathetic Nervous System/metabolism , Synapses/metabolism , Yohimbine/pharmacologyABSTRACT
O hidrogênio maleato de lisurida é de um novo derivado semi-sintético do ergot. Apresenta propriedades agonista dopaminérgico e antagonista seratoninérgico. É cerca de dez vezes mais potente potente que a bromoergocriptina e apresenta a vantagem adicional de possuir estrutura molecular mais simples, sem cadeia peptídica lateral, o que lhe assegura menor custo de síntese e de tratamento. Seis mulheres, portadoras da galactorréia e hiperprolactinemia, foram tratadas com a droga na dose máxima de 0,3mg/dia por 30 dias ou de 0,4mg/dia por 60 dias. A prolactina foi reduzida a níveis normais em 4 pacientes. A galactorréia cessou em todas, ciclos menstruais ocorreram em duas. A cefaléia foi melhorada em uma. Houve boa tolerància do medicamento.