Ganglionic blockers inhibit autonomic activity by blocking nicotinic receptors in the autonomic ganglia, suppressing impulse transmission. These blockers lack selectivity between sympathetic and parasympathetic ganglia and are ineffective as neuromuscular junction antagonists. They can be categorized into two groups:

1. Prototype Nicotine: These agents stimulate ganglia through acetylcholine-like action, leading to consistent depolarization and subsequent ganglionic blockade.
2. Competitive Antagonists: Agents like trimethaphan and mecamylamine compete with acetylcholine for binding to nicotinic receptors, thereby preventing impulse transmission. This category includes nondepolarizing, competitive antagonists that can elicit unpredictable responses.

Ganglionic blockers have erratic and incomplete absorption, and their ionization hinders cell membrane permeation. Mecamylamine can cross the blood-brain barrier. Kidneys primarily excrete these agents unchanged. Due to their impact on both the sympathetic and parasympathetic divisions, ganglionic blockers produce diverse effects. Sympathetic blockage results in a significant drop in blood pressure due to arterial vasodilation and the blockage of cardiovascular reflexes. Postural hypotension, leading to fainting from a sudden decrease in arterial pressure, is an expected outcome. Ganglionic blockers also cause postexercise hypotension, inhibit sympathetic activity, and reduce vasoconstriction of dilated arteries. While cerebral blood flow reduction is minimal, skeletal muscle blood flow remains unchanged, and renal and splanchnic blood flow decreases.

The clinical relevance of ganglionic blockers has declined due to associated side effects and the availability of safer alternatives. Currently, no agents are commercially marketed, but they may still be occasionally used for managing hypertensive emergencies. In pharmacology, these blockers serve as valuable experimental tools. Adverse effects include prolonged neuromuscular blockade, constipation, hypotension, dry mouth, urinary retention, syncope, and cycloplegia.