What is the mechanism of action of dicyclomine?

Dicyclomine Mechanism of Action

Dicyclomine relieves gastrointestinal smooth muscle spasm through a dual mechanism: anticholinergic blockade at muscarinic acetylcholine receptors (approximately 1/8th the potency of atropine) and direct smooth muscle relaxation (musculotropic effect). 1

Primary Mechanisms

Anticholinergic (Antimuscarinic) Activity

• Dicyclomine acts as a competitive antagonist at muscarinic acetylcholine receptors, blocking the binding of acetylcholine at receptor sites 1
• The drug demonstrates selective affinity for M1 muscarinic receptor subtypes (pA2 9.13) compared to M2 receptors (pA2 7.21-7.61), making it approximately 100-fold more selective for M1 receptors 2, 3
• This M1 selectivity distinguishes dicyclomine from non-selective agents like atropine, though it remains less selective than pirenzepine 3
• In functional studies, dicyclomine shows 10-fold greater ability to inhibit M1-mediated ganglionic responses compared to peripheral muscarinic responses in heart and smooth muscle 3

Direct Smooth Muscle (Musculotropic) Effect

• Dicyclomine directly antagonizes smooth muscle spasm independent of cholinergic pathways, as demonstrated by its ability to block bradykinin- and histamine-induced spasms in isolated guinea pig ileum 1
• Atropine cannot block these non-cholinergic spasms, confirming dicyclomine's unique direct muscle-relaxing properties 1
• In vivo studies show dicyclomine equally potent against both acetylcholine-induced and barium chloride-induced intestinal spasm, while atropine is 200 times more potent against acetylcholine than barium chloride 1

Comparative Potency and Selectivity

Anticholinergic Potency Profile

• Dicyclomine is approximately 1/8th as potent as atropine at antimuscarinic sites in vitro 1
• For mydriatic (pupil dilation) effects: approximately 1/500th as potent as atropine 1
• For antisialagogue (saliva reduction) effects: approximately 1/300th as potent as atropine 1
• The rank order of M1 selectivity is: pirenzepine > dicyclomine > trihexyphenidyl > atropine 3

Tissue-Specific Effects

• In bladder smooth muscle, dicyclomine shows competitive inhibition of acetylcholine-induced contractions, with effects most marked in bladder body, moderate in bladder base, and minimal in proximal urethra 4
• Dicyclomine fails to inhibit barium chloride-induced contractions in guinea pig vesicourethral smooth muscle but shows significant antagonism in rabbit bladder tissue 4

Pharmacodynamic Effects

Dicyclomine's anticholinergic properties produce multiple systemic effects including:

• Inhibition of saliva and sweat secretion 1
• Decreased gastrointestinal secretions and motility 1
• Drowsiness 1
• Pupillary dilation 1
• Increased heart rate 1
• Depressed motor function 1

Clinical Implications

Appropriate Indications

• Dicyclomine is primarily indicated for gastrointestinal smooth muscle spasm in irritable bowel syndrome (IBS), not for gastritis 5
• The American Gastroenterological Association conditionally recommends antispasmodics like dicyclomine for IBS-related abdominal pain 6
• Antispasmodics provide adequate global relief of IBS symptoms (RR 0.67; 95% CI 0.55-0.80) and improvement in abdominal pain (RR 0.74; 95% CI 0.59-0.93) compared to placebo 6

Limitations from Mechanism

• Anticholinergic side effects (dry mouth, dizziness, blurred vision) may limit use, particularly in constipation-predominant conditions 6, 7
• The dual mechanism provides both benefits (broader smooth muscle relaxation) and drawbacks (more systemic anticholinergic effects than pure musculotropic agents) 1
• Elderly patients are more susceptible to anticholinergic side effects and require careful monitoring 7