PMID- 1358421
OWN - NLM
STAT- MEDLINE
DCOM- 19921223
LR  - 20190720
IS  - 0008-4212 (Print)
IS  - 0008-4212 (Linking)
VI  - 70
IP  - 6
DP  - 1992 Jun
TI  - Yohimbine-precipitated clonidine withdrawal: an experimental model of the 
      antihypertensive drug withdrawal syndrome.
PG  - 853-8
AB  - In this study, a model of the clonidine withdrawal syndrome in normotensive rats 
      was used to investigate the mechanisms and sites of the cardiovascular responses 
      associated with this withdrawal. Clonidine (400 micrograms.kg-1.day-1), an alpha 
      2-adrenergic receptor agonist, was administered to rats via indwelling osmotic 
      minipumps for 7 days. Withdrawal was precipitated by an intravenous injection of 
      the alpha 2-adrenergic receptor antagonist yohimbine under alpha-chloralose 
      anaesthesia, and the blood pressure and heart rate responses were recorded. 
      Yohimbine (0.25, 0.50, and 1.0 mg/kg i.v.) in clonidine-treated rats provoked an 
      immediate rise in blood pressure and heart rate. Similar injections in 
      saline-treated rats produced slight hypotension and modestly increased the heart 
      rate. Intracerebroventricular (i.c.v.) yohimbine injection (30 or 120 
      micrograms/kg in 10 microL volume) failed to elicit signs of withdrawal in 
      clonidine-treated animals, but a subsequent intravenous injection of yohimbine 
      (0.5 mg/kg) provoked brisk signs of withdrawal. hexamethonium (2 mg/kg) 
      pretreatment did not abolish the increase in the heart rate, but it delayed the 
      blood pressure increase. Pretreatment with atropine sulfate (1 mg/kg) did not 
      block the yohimbine-induced increase in heart rate or blood pressure. This study 
      demonstrates that yohimbine can effectively produce cardiovascular signs of 
      withdrawal in rats chronically exposed to clonidine. The lack of i.c.v. yohimbine 
      suggests that the antagonist-precipitated withdrawal may not have a central 
      origin.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Penning, D H
AU  - Penning DH
AD  - Department of Anaesthesia, Faculty of Medicine, Queen's University, Kingston, 
      Ont., Canada.
FAU - Jhamandas, K
AU  - Jhamandas K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Canada
TA  - Can J Physiol Pharmacol
JT  - Canadian journal of physiology and pharmacology
JID - 0372712
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Ganglionic Blockers)
RN  - 0 (Hexamethonium Compounds)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 3C9PSP36Z2 (Hexamethonium)
RN  - 7C0697DR9I (Atropine)
RN  - MN3L5RMN02 (Clonidine)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Animals
MH  - Antihypertensive Agents/*adverse effects
MH  - Atropine/pharmacology
MH  - Blood Pressure/drug effects
MH  - Central Nervous System/drug effects/physiology
MH  - Choline/antagonists & inhibitors/physiology
MH  - Clonidine/*adverse effects
MH  - Ganglia, Sympathetic/drug effects/physiology
MH  - Ganglionic Blockers/pharmacology
MH  - Heart Rate/drug effects
MH  - Hexamethonium
MH  - Hexamethonium Compounds/pharmacology
MH  - Injections, Intravenous
MH  - Injections, Intraventricular
MH  - Male
MH  - *Models, Biological
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substance Withdrawal Syndrome/drug therapy/*etiology/physiopathology
MH  - Yohimbine/*pharmacology
EDAT- 1992/06/01 00:00
MHDA- 1992/06/01 00:01
CRDT- 1992/06/01 00:00
PHST- 1992/06/01 00:00 [pubmed]
PHST- 1992/06/01 00:01 [medline]
PHST- 1992/06/01 00:00 [entrez]
AID - 10.1139/y92-114 [doi]
PST - ppublish
SO  - Can J Physiol Pharmacol. 1992 Jun;70(6):853-8. doi: 10.1139/y92-114.