In this study we investigated the effects of
antimuscarinics with different selectivity on the intestinal migrating myoelectric complex (MMC) in five fasting, conscious dogs, chronically fitted with
electrodes along the small bowel. Furthermore, we evaluated the chronotropic and
mydriatic effects to assess the in vivo selectivity of the agents tested. Dose-response studies were performed with the following drugs administered i.v.:
atropine,
telenzepine (M1 antagonist),
AF-DX 116 [11,2-(diethylamino)methyl-1-piperidinyl-acetyl-5,11-dihydro-6H-pyrido-2 ,3b- 1,4-benzodiazepine-6-one (M2 antagonist)] and 4-diphenylacetoxy-N- methylpiperidine methiodide (4-DAMP) (M3 antagonist). All the
antimuscarinics tested dose-dependently increased the duration of the MMC period and inhibited spike activity, except low-dose
telenzepine (3-10 nmol/kg), which shortened the MMC period and stimulated spike activity. High-dose
telenzepine (> 100 nmol/kg) mimicked the inhibitory effect of
atropine on the intestine. ED50 values for delay of MMC onset were 87,232, > 10,000 and 129 nmol/kg for
atropine,
telenzepine,
AF-DX 116 and
4-DAMP, respectively. At doses lengthening the MMC period,
atropine and
4-DAMP also induced
tachycardia and
mydriasis. At doses shortening the MMC period,
telenzepine had no effect on pupil diameter or heart rate, except at the dose of 10 nmol/kg, which reduced heart rate. Finally,
AF-DX 116, at doses inducing marked
tachycardia, had a minor intestinal effect and no
mydriatic effect. The present data are consistent with the hypothesis that both M1 and M3 receptors are involved in the regulation of the MMC: M1 receptors are probably located on an inhibitory pathway, whereas M3 receptors mediate excitatory stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)