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. 1994 Nov;113(3):1071–1077. doi: 10.1111/j.1476-5381.1994.tb17102.x

The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol.

W Rouse 1, P J Stafford 1, I R Johnson 1
PMCID: PMC1510440  PMID: 7858851

Abstract

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows heart rate. 2. The haemodynamic effects of ZD7288 (0.1, 0.3 and 1.0 mg kg-1, i.v.) have been evaluated and compared with those of placebo (physiological saline), zatebradine (ULFS 49, 0.1, 0.3 and 1.0 mg kg-1, i.v.) and propanolol (0.03, 0.1, and 0.3 mg kg-1, i.v.) in beagles chronically instrumented for measurement of heart rate, aortic pressure, aortic flow and dPLV/dtmax. The dogs were trained to run at 6.5 k h-1 on a level treadmill for 5 min at half hourly intervals over a period of 4 h. Drugs were dosed cumulatively after the second, fourth and sixth exercise periods. 3. Control experiments demonstrated a degree of accommodation to repeated exercise over a period of 4 h. Resting heart rate decreased by 21 beats min-1, but heart rate response to exercise was maintained, whereas dPLV/dtmax at rest remained steady while the response to exercise decreased significantly (by 25% after 2 h, P < 0.05). 4. ZD7288 and zatebradine both decreased heart rate during exercise in a dose-dependent manner, whilst heart rate at rest did not differ from resting heart rates in saline dosed control animals. In contrast, heart rate at rest and during exercise were lowered equally by the lowest doses of propranolol (approximately by 30 beats min-1), and additional doses caused only minor additional decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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