Investigations into the bradycardic action of indoramin. 1985

C Lillie, and D W Harron, and W Kobinger

Indoramin is a selective alpha 1-antagonist which reduces blood pressure without reflex tachycardia and can cause a bradycardia. The direct bradycardic effect of indoramin was investigated in various isolated cardiac preparations as well as in the intact cat. In isolated guinea-pig atria indoramin reduced spontaneous atrial rate in concentrations similar to those that reduced maximal driving frequency but smaller than those reducing contractility (EC30 = 0.9, 1.3 and 5.2 micrograms/ml, respectively). In the isolated perfused electrically driven (2.5 Hz) guinea-pig heart, indoramin 1 microgram/ml mainly increased ST interval with no effect on QRS interval, higher concentrations (3 micrograms/ml) also increased the QRS interval. In anaesthetized cats indoramin 6 mg/kg i.v. reduced blood pressure and heart rate (increased cycle length), increased the ST interval and effective refractory period (measured by electrical stimuli from the right ventricle) but had little or no effect on the QRS interval and the diastolic stimulation threshold. With the 10 mg/kg dose the latter two parameters were increased. Analogous experiments with the antiarrhythmic drug mexiletine (class I) showed little changes in cycle length, effective refractory period and the ST interval, however, there was a marked increase in diastolic threshold. DL-sotalol, which as well as having a beta-adrenoceptor blocking action, also prolongs action potential duration (class III antiarrhythmic activity), had the same cardiac profile as indoramin. For both indoramin and sotalol a significant positive correlation was shown between increase in cycle length and increase in effective refractory period. It is suggested that indoramin exerts class III antiarrhythmic activity and that this property is responsible for the bradycardic action of the drug which is seen in doses that already markedly reduce blood pressure. In higher doses or concentrations indoramin also exerts class I antiarrhythmic activity which, however, does not contribute to the bradycardic effect.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007217 Indoramin An alpha-1 adrenergic antagonist that is commonly used as an antihypertensive agent. Wy-21901,Wy 21901,Wy21901
D008297 Male Males
D008801 Mexiletine Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties. KO-1173,KO1173,KOE-1173,Mexiletene,Mexiletine Hydrochloride,Mexitil,Mexitil PL,Mexityl,Novo-Mexiletine,KO 1173,KOE 1173,KOE1173,Novo Mexiletine
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002415 Cats The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801) Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D003326 Coronary Circulation The circulation of blood through the CORONARY VESSELS of the HEART. Circulation, Coronary
D004562 Electrocardiography Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY. 12-Lead ECG,12-Lead EKG,12-Lead Electrocardiography,Cardiography,ECG,EKG,Electrocardiogram,Electrocardiograph,12 Lead ECG,12 Lead EKG,12 Lead Electrocardiography,12-Lead ECGs,12-Lead EKGs,12-Lead Electrocardiographies,Cardiographies,ECG, 12-Lead,EKG, 12-Lead,Electrocardiograms,Electrocardiographies, 12-Lead,Electrocardiographs,Electrocardiography, 12-Lead
D005260 Female Females

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