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In vitro cardiac effects and antiarrhythmic properties of guanfacine.

Guanfacine (Estulic, Tenex), a centrally acting antihypertensive, was investigated for its effects on the heart using isolated cardiac preparations and in patients for antiarrhythmic properties. The tachycardic effects of sympathetic nerve stimulation in spontaneously beating atria were concentration-dependently suppressed by guanfacine. A 50% inhibition was observed in atria from Syrian hamsters, guinea-pigs and rabbits with 1, 5.4 and 20 nmol/l, respectively. In guinea-pig atria the concentration-response curve of guanfacine was shifted to the right in a parallel manner by rauwolscine (pA2 8.58) but was not displaced by prazosine 1 mumol/l. In rabbit right papillary muscles guanfacine 1 to 10 mumol/l increased force of contraction by 13 to 91%. The positive inotropic effect was antagonized by prazosine 1 mumol/l but was not influenced by cimetidine 1 mumol/l or rauwolscine 1 mumol/l. It is concluded that guanfacine activates cardiac postsynaptic a1- and neuronal presynaptic a2-adrenoceptors with a preference to the latter of about 2 orders of magnitude. Direct membrane stabilizing effects in guinea-pig atria were negligible. In 4 patients with coronary heart disease associated with arrhythmia guanfacine 1 mg per day during 10 days decreased ventricular premature contractions, couplets and abolished appearance of ventricular tachycardias. These preliminary clinical results indicate that guanfacine may reduce cardiac risk factors.

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