• Acetylcholine is the endogenous agonist of cholinergic receptors (i.e. nicotinic and cholinergic receptors) and is secreted by cholinergic neurons in the CNS, autonomic ganglia, adrenal medulla, and the neuromuscular junction. It can also be administered as a drug although its broad-ranging actions render it of very limited therapeutic value. Our review the pharmacological effects of acetylocholine is primarily with the goal of better understanding the physiological actions of this neurotransmitter.
Pharmacological Targets
Pharmacological Effects
  • Overview
    • The primary effects intravenous administration of ACh are on the cardiovascular system, yielding negative chronotropic, dromotropic, and inotropic effects as well as a vasodilatory reduction in blood pressure. Although ACh activates both nicotinic and muscarinic receptors, these effects are primarily caused by activation of muscarinic receptors. ACh is rapidly inactivated by synaptic and soluble cholinesterases, rendering if pharmacological actions very short-lived.
  • Cardiac Effects
    • Administration of ACh mimics the cardiac effects of the parasympathetic nervous system with reduced contractility, sinus rate, and AV nodal conduction. The result is reduced cardiac output and heart rate.
  • Vascular Effects and Blood Pressure
    • Intravenous injection of ACh results in vasodilation apparently by eliciting release of nitric oxide and thus activating the nitric oxide mechanism of local blood flow regulation. This reduces systemic vascular resistance and in the context of reduced cardiac output, described above, combines to produce a drop in systemic arterial pressure, yielding hypotension
    • This effect of ACh appears to be mediated by cholinergic receptors on the vascular wall itself. However, there is little evidence for any substantial physiological role of these vascular ACh receptors as acetylcholine is not released in soluble form in the systemic circulation. Thus, this appears to be a phenomenon purely as a result of pharmacological administration of ACh.
  • GI and GU Effects
    • Theoretically one would expect activation of muscarinic receptors in the GI and GU tract to enhance GI secretions, GI Motility, as well as boost contraction of the bladder's detrusor muscle, thus promoting mictruition. However, these effects are inconsistently seen during systemic administration of ACh likely due to rapid inactivation of ACh by cholinesterases prior to their reaching visceral organs.
  • Ocular Effects
    • When administered by eye drops, ACh induces mioisis by enhancing contraction of the pupillary sphincter muscle.
Therapeutic Uses
  • There are almost no contemporary therapeutic uses for acetylcholine due to its rapid inactivation by cholinesterases and its diverse non-specific effects as described above. Longer-acting direct cholinergic agonists include bethanochol, carbachol, and pilocarpine.