Description

Drotaverine is a potent, non-anticholinergic spasmolytic (antispasmodic) agent. It is a derivative of isoquinoline and is known for its direct action on the smooth muscles of the gastrointestinal, biliary, urinary, and reproductive systems. Unlike some other antispasmodics, it does not act on the central nervous system or have significant anticholinergic side effects. It is available in oral tablets and injectable forms.

Indication

Drotaverine is indicated for the symptomatic relief of spasms and pain associated with smooth muscle contractions. Its main indications include:

• Biliary Colic: To relieve spasms associated with cholelithiasis (gallstones), cholecystitis, or cholangitis.

• Renal Colic: To relieve pain and spasms associated with nephrolithiasis (kidney stones) and other urinary tract conditions.
• Gastrointestinal Spasms: For spasms of the smooth muscles of the stomach, intestines, and colon, such as in irritable bowel syndrome (IBS) or spastic constipation.

• Gynecological Spasms: To relieve painful menstrual cramps (dysmenorrhea).

• Headaches: May be used for tension-type headaches that have a muscular component.

Mechanism of Action

The mechanism of action of drotaverine is based on its direct relaxant effect on smooth muscles, which is mediated by its selective inhibition of a key enzyme.

1. Phosphodiesterase (PDE) Inhibition: Drotaverine’s primary mechanism is the potent and selective inhibition of the enzyme phosphodiesterase type IV (PDE4). PDE4 is the predominant phosphodiesterase isozyme in smooth muscle tissue.
2. Increased cAMP Levels: PDE4 is responsible for breaking down cyclic adenosine monophosphate (cAMP) into inactive AMP. By inhibiting PDE4, drotaverine causes an increase in intracellular levels of cAMP.

3. Inhibition of Muscle Contraction: The increased level of cAMP triggers a series of intracellular events that lead to smooth muscle relaxation. Specifically, it activates an enzyme called protein kinase A (PKA). PKA then phosphorylates and inactivates myosin light chain kinase (MLCK).
4. Smooth Muscle Relaxation: MLCK is the enzyme responsible for phosphorylating the myosin light chain, a necessary step for smooth muscle contraction. By inhibiting MLCK, drotaverine prevents the phosphorylation of the myosin light chain. This disruption of the contractile process leads to the relaxation of the smooth muscle, effectively relieving spasms and associated pain.

The direct and specific action on smooth muscles, independent of the autonomic nervous system, makes drotaverine a targeted and effective antispasmodic.