B. Schade et C. Studenik, Effects of novel pyridothiazepines and pyridothiazines on contractility ofisolated guinea-pig heart muscle and vascular smooth muscle preparations, BIOL PHAR B, 22(7), 1999, pp. 683-686
The effects of newly synthesized pyridothiazepines MM 4 (1-[N-[2-(3,4-dimet
hoxy-phenyl)ethyl]-N-methyl-aminoacetyl]-1,2,3,4-tetrahydro-pyrido[2,3-b][1
,4]thiazepine fumarate), MM 6 (1-[N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methyl
aminopropionyl]-1,2,3,4-tetrahydro-pyrido[2,3-b][1,4] thiazepine fumarate)
and the novel pyridothiazines MM 10 (2,3-dihydro-1-[N-[2-(3,4-dimethoxyphen
yl)ethyl]-N-methylaminoacetyl]-1H-pyrido[2,3-b][1,4]thiazine fumarate) and
MM 11 (2,3-dihydro-1-[N-[2-(3,4-dimethoxy-phenyl)ethyl]-N-methylaminopropio
nyl]-1H-pyrido[2,3-b][1,4]thiazine fumarate) on the contractility of isolat
ed papillary muscles and aortic preparations of guinea pigs were studied us
ing isometric contraction force measurements. The EC50 values for the negat
ive inotropic effect were 27 mu mol/l (MM 4), 19 mu mol/l (MM 6), 32 mu mol
/l (MM 10) and 24 mu mol/l (MM 11). In K+-precontracted aortic rings ([K+](
o) 60 mmol/l), the compounds induced relaxation with EC50 values of 27 mu m
ol/l (MM 4), 24 mu mol/l (MM 6), 84 mu mol/l (MM 10) and 68 mu mol/l (MM 11
). Pyridothiazepines as well as pyridothiazines (100 mu mol/l) were able to
depress norepinephrine bitartrate (NE 10 mu mol/l)-induced contraction of
aortic rings in a calcium-free solution. It was concluded that the investig
ated compounds exert calcium antagonistic properties in both cardiac and sm
ooth muscle. This antagonistic effect might be due to the inhibition of tra
nsmembrane calcium influx and/or intracellular calcium release.