Clinical pharmacology of terodiline.
Bladder contraction in man, both in normal subjects and in patients with unstable bladder seem to be mainly parasympathetically mediated. However, treatment of unstable bladder patients with anticholinergics is often an ineffective form of treatment. Drugs inhibiting bladder contraction by a combined anticholinergic and calcium entry blocking action offer a theoretically attractive effect profile. One such drug is terodiline. The pharmacodynamic effects and the pharmacokinetics of the drug are briefly reviewed. Terodiline has non-selective anticholinergic and calcium blocking effects within the same concentration range, the anticholinergic effect predominating at low and the calcium entry blocking action at high concentrations. Terodiline is well absorbed from the gastrointestinal tract, and has a bioavailability of 90%. The volume of distribution is approximately 500 litres, metabolism extensive, and serum half-life about 60 hours. The therapeutic range of plasma concentrations has not been established, but side effects are often encountered at concentrations exceeding 600 micrograms/l. It is concluded that the pharmacodynamic effect profile and the pharmacokinetics of terodiline makes it an interesting alternative to drugs currently used for inhibition of bladder contraction.
D000818:Animals; D002082:Butylamines / Q000378:metabolism / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology; D011817:Rabbits; D001743:Urinary Bladder / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D002082:Butylamines; D002121:Calcium Channel Blockers; D010276:Parasympatholytics; C010637:terodiline