新しい抗真菌剤cis-liACety1-4[4-[[2-(2, 4-diChlorOphenyl)-2-(1H-imidazol-lylmethyl)-1, 3-dioxolan-4-y1]methoxy] phenyl] piperazineの一般薬理作用
1982 年 35 巻 6 号 p. 1629-1648
詳細
1982 年 35 巻 6 号 p. 1629-1648
General pharmacological effects of KW-1414, a new orally-active antifungal agent, were studied, and the following results were obtained.
1. KW-1414400mg/kg, p.o.caused significant depression on spontaneous activity, prolongation of pentobarbital sodium induced hypnosis, hypothermia and augmentation of reserpine-induced hypothermia in mice.In addition, KW-1414400mg/kg, p.o.showed slight muscle relaxant and anticonvulsive activities in mice.Ptosis and slight passivity were also observed at this dose.But KW-1414100mg/kg, p.o.caused only augmentation of reserpine-induced hypothermia, and any of the above effect was not found at the dose of25mg/kg, p.o.KW-141410mg/kg, i.v.had no effect on body temperature in rats and mice, on spontaneous EEG in rabbits and on spinal reflex in cats.
2. KW-14143mg/kg, i.v.lowered femoral blood pressure, increased femoral blood flow transiently and decreased heart rate in dogs.In isolated atria of guinea pigs, KW-1414 10-4M decreased atrial rate and atrial contractile force significantly.But KW-1414had no effect on respiratory rate, ECG and blood pressure reflex induced by bilateral carotid artery occulusion and asphyxia in dogs at the dose of10mg/kg, i.v.KW-1414100mg/kg, p.o.also had no effect on heart rate in conscious rabbits. And KW-1414 10-4m did not influenced hemolysis and hemopexis in rabbit blood.
3. KW-1414caused dose-dependently contraction of nictitating membrane induced by adrenaline hydrochloride injection, but had no effect on that induced by electric stimulation in cats.And KW-1414 10mg/kg, i.v.had no effect on pressure-response induced by noradrenaline or acetylcholine chloride injection.
4. KW-1414at high doses had non-specific depression on contraction of isolated smoo th muscles induced by various agonists and on spontaneous movement of isolated smooth muscles. And KW-1414 10-4m caused relaxation of isolated tracheal smooth muscle of guinea pigs.But KW-1414had no effect on intestinal propulsion in mice.
5. KW-1414 10-4M augmented the contraction of isolated phrenic nerve-diaphragm preparation induced by electric stimulation in rats.But KW-141410mg/kg, i.v.scarcely influenced the contraction of tibialis anterior muscle-sciatic nerve preparation induced by electric stimulation in rabbits.
6. KW-1414decreased urinary volume and electrolyte excretion in rats dose-dependently, while it had no local anesthetic activity in guinea pigs.And KW-1414had no effect on gastric secretion, on spontaneous bile excretion in rats and on dermal tissue permeability in rabbits.
