Withdrawal reactions following cessation of central alpha-adrenergic receptor agonists

Hypertension. 1984 Sep-Oct;6(5 Pt 2):II71-5. doi: 10.1161/01.hyp.6.5_pt_2.ii71.


Interruption of long-term treatment with alpha 2-adrenergic receptor agonists may be associated with reversal of their hemodynamic effects, clinical and biochemical evidence of increased peripheral sympathetic activity, and behavioral responses similar to those seen after narcotic or alcohol withdrawal. Reactions are most commonly observed after short-acting imidazoline drugs such as clonidine and tiamenidine. Reactions are less common after longer acting agents such as guanfacine. A new management approach to withdrawal has been evaluated, which uses a combination of alpha 1-blockade (prazosin) and cardioselective beta-blockade (atenolol) together with a benzodiazepine (chlordiazepoxide). Withdrawal reactions were not observed in eight patients in whom clonidine was withdrawn under cover of these agents. The mechanism of the withdrawal reaction may involve agonist-induced down regulation of alpha 2-adrenergic receptor affinity, number, or both. Experimental studies with the irreversible alpha-antagonist phenoxybenzamine on the turnover of alpha 2-receptors suggest that recovery of receptor number may be much slower in the brain than in the periphery.

Publication types

  • Review

MeSH terms

  • Adrenergic alpha-Agonists / adverse effects*
  • Adrenergic alpha-Antagonists / therapeutic use
  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Animals
  • Antihypertensive Agents / adverse effects
  • Benzodiazepines / therapeutic use
  • Blood Pressure
  • Brain / metabolism
  • Chlordiazepoxide / therapeutic use
  • Clonidine / adverse effects
  • Clonidine / metabolism
  • Female
  • Guanfacine
  • Guanidines / adverse effects
  • Heart Rate
  • Humans
  • Hypertension / chemically induced
  • Male
  • Methyldopa / adverse effects
  • Middle Aged
  • Phenoxybenzamine / pharmacology
  • Phenylacetates / adverse effects
  • Prazosin / metabolism
  • Rabbits
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / physiology
  • Substance Withdrawal Syndrome* / physiopathology
  • Substance Withdrawal Syndrome* / prevention & control
  • Thiophenes / adverse effects


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Guanidines
  • Phenylacetates
  • Receptors, Adrenergic, alpha
  • Thiophenes
  • Phenoxybenzamine
  • Benzodiazepines
  • tiamenidine
  • Guanfacine
  • Methyldopa
  • Chlordiazepoxide
  • Clonidine
  • Prazosin