The withdrawal of centrally acting antihypertensives in dogs.
1. The effects of the withdrawal of clonidine and 6-(2-chloro-6-fluoro-phenyl)-2,3,6,7-tetrahydro-5H-pyrrolo-(1,2-a)-imidazole hydrobromide (ICI 106270) on the blood pressure and heart rate of chronically dosed beagle dogs has been investigated. 2. The control heart rate was 75.4 beats/min and it varied considerably during therapy with clonidine (100-200 microgram/kg orally 2 X or 3 X daily for 10 days). 3 h after dosing it was always depressed, this reduction varying from 48.5% on day 1 to 32.2% on day 9. The heart rate was depressed 8 h after the initial dose but by day 9 heart rate was 37.6% above control at this time. 3. On withdrawal of clonidine heart rate displayed a marked rebound which reached a maximum of 59.9% above control 16 h after the last dose. 4. During clonidine treatment diastolic blood pressure fell by 23.3% from a control of 87.4 mmHg and on withdrawal it returned to control with no overshoot. 5. During treatment with ICI 106270 (600 microgram/kg orally 3 X daily for 10 days) heart rate did not rise above the control level of 88.9 beats/min and diastolic blood pressure was decreased 21.6% from a control value of 113.7 mmHg. 6. On withdrawal of ICI 106270 both blood pressure and heart rate returned to control levels without any overshoot. 7. The tachycardia on withdrawal of clonidine in dogs occurred with every animal treated and may represent a useful model for assessing the likelihood of other centrally acting antihypertensives to produce rebound in man. In this test situation ICI 106270 did not produce rebound tachycardia.
D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000009:adverse effects; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects; D008297:Male; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013997:Time Factors
D000959:Antihypertensive Agents; D007093:Imidazoles; C032860:ICI 106270; D003000:Clonidine