This chapter is relevant to Section M2(i) of the 2023 CICM Primary Syllabus, which expects the exam candidates to “understand the pharmacology of drugs acting upon the autonomic nervous system”. From past papers and syllabus pharmacopoeia items we can infer that what they really mean by this is "acetylcholinesterase inhibitors and anticholinergic drugs"; but that does not mean that agents acting on the sympathetic nervous system can be completely forgotten. Rather, they are distributed to the cardiovascular system, as that is where their effect is mostly felt; and to include them here is therefore an exercise in satisfying the author's neurotic need for completeness (because if you have a sympathomimetic chapter, then surely there should also be a sympatholytic one). In that spirit, this section on sympatholytic agents is presented to the reader, with the expectation that the weary exam candidate will recognise that their time is being wasted, and navigate away towards higher mark-scoring sections such as beta-blockers,  miscellaneous antihypertensives, clonidine or dexmedetomidine

What exactly is a “sympatholytic"?

Along "sympathomimetic", this word has sufficient support to appear in IUPAC glossaries, and their official definition is:

  1.  adj., Blocking transmission of impulses from the adrenergic (sympathetic) postganglionic fibers to effector organs or tissues.
  2. n., Agent that blocks transmission of impulses from the adrenergic (sympathetic) postganglionic fibers to effector organs or tissues.

    SN anti-adrenergic 

So, the opposite of "sympathomimetic", i.e. these are drugs that make it look like your sympathetic nervous system has been suppressed or deactivated. Just like the activation of the sympathetic nervous system, this is something that could happen at a variety of different levels, from the CNS to the peripheral receptors, and though there is no official classification framework for these drugs most authors use that CNS-receptor axis to orient their taxonomies. For example, Engelman (1988) lists five major classes, vaguely along these lines:

The attentive reader will at this stage point out that, if the intention was to offer a brief sketch of these drugs which skims over important details and is otherwise devoid of strong educational content, then the chapter on miscellaneous antihypertensives already does that (and it is still much more attention than they deserve from a CICM exam standpoint). In summary, all that is required here is this short overview:

  • Sympatholytic agents are those that inhibit the activation of the sympathetic nervous system
  • For many of them, the side effect profile has prevented widespread use
  • Central sympathetic depressants 
    • Inhibit central regulation of sympathetic nerve activity, mostly by presynaptic α2-agonist effect which downregulates noradrenaline release.
    • Side effect profile includes CNS effects such as sedation and depression 
    • Examples:
      • Clonidine
      • Methyldopa
  • Ganglionic blockers
    • Inhibit ganglionic autonomic neurotransmission by effects on the nicotinic ganglionic receptor, therefore decreasing both sympathetic tonic input to the vascular smooth muscle, and to the myocardium. Also block vagal neurotransmission.
    • Parasympathetic blockade effects have been the major barrier to use, including dry mouth, constipation, cycloplegia, urinary retention, and sexual dysfunction
    • Examples:
      • Hexamethonium
      • Trimethaphan
  • Catecholamine synthesis inhibitors
    • Prevent the production of catecholamine neurotransmitters
    • Also active in the CNS, which produces sedation fatigue and depression.
    • Examples:
      • Methyldopa
      • Methyltyrosine
  • Catecholamine reuptake and storage antagonists
    • Reduce the storage of catecholamine neurotransmitters by preventing reuptake or by displacing them from their storage vesicles
    • Have all the side effects expected from CNS-active agents (eg. sedation, depression, reduced mental acuity), combined with a very slow onset of effect (2-4 weeks). 
    • ​​​​​​​Examples:
      • Reserpine
      • Guanethedine
      • Guanadrel
  • Adrenergic receptor antagonists
    • Directly anatagonise the effect of noradrenaline and adrenaline at their peripheral receptors, by competitive inhibition
    • Most common and most popular sympatholytic agents because they mostly lack major CNS effects and because their receptor selectivity allows a more targeted sympathetic effect
    • Examples:


DeQuattro, V., and D. Li. "Sympatholytic therapy in primary hypertension: a user friendly role for the future." Journal of human hypertension 16.1 (2002): S118-S123.

Vongpatanasin, Wanpen, et al. "Central sympatholytic drugs." The Journal of Clinical Hypertension 13.9 (2011): 658.

McComb, Meghan N., James Y. Chao, and Tien MH Ng. "Direct vasodilators and sympatholytic agents.Journal of cardiovascular pharmacology and therapeutics 21.1 (2016): 3-19.

Engelman, K. A. R. L. "Side effects of sympatholytic antihypertensive drugs." Hypertension 11.3_pt_2 (1988): II30.