Lidamidine HCl has been suggested to be effective in treating certain
motor disorders of the gastrointestinal tract.
Lidamidine has alpha-2 agonist as well as
local anesthetic properties. We studied the antimotility and
antidiarrheal activity of
WHR 1049, a hepatic metabolite of
lidamidine known to have some activity and to persist longer in the serum than does
lidamidine. We recorded the intestinal myoelectric activity of fasted unanesthetized rats with bipolar
electrodes implanted on their proximal jejunum. We found that
lidamidine HCl, given by gavage, inhibited fasting myoelectric activity in a dose-dependent manner (using 0.5-4.0 mg/kg). Neither saline nor
tetracaine inhibited myoelectric activity.
WHR 1049 given by gavage also inhibited myoelectric activity and was 30 times as potent as
lidamidine (milligram per milligram, using 0.0625- to 0.25-mg/kg doses). Pretreatment with
yohimbine (5 mg/kg s.c.), before administration of
WHR 1049, decreased the myoelectric activity inhibition by two-thirds (but did not completely block it).
Castor oil (1 ml/200 g b.wt.) was given to induce
diarrhea and did so when given alone or with saline (vehicle) pretreatment. When these animals were pretreated with 0.25 mg/kg of
WHR 1049, the same dose of castrol oil did not induce
diarrhea for a 6-hr observation period. We conclude that
WHR 1049 is a potent metabolite of
lidamidine that inhibits myoelectric activity, has significant alpha-2 agonist activity and blocks induced
diarrhea. Because
tetracaine does not inhibit myoelectric activity we suggest that the
local anesthetic properties of
lidamidine do not account for any of the myoelectric activity inhibition.
WHR 1049 may account for much of the antimotility and
antidiarrheal activity of
lidamidine.