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  • Title: [Phamacolofical studies of ifenprodil].
    Author: Maeda Y, Furukawa T.
    Journal: Nihon Yakurigaku Zasshi; 1975 Sep; 71(6):585-95. PubMed ID: 1238329.
    Abstract:
    Pharmacological effects of ifenprodil (IP), 4-benzyl-alpha-(p-hydroxyphenyl)-beta-methyl-1-piperidineethanol-L-(+)-tartrate monohydrate (Funai Pharmaceutical), a potential vasodilator, were studied in the dog, rabbit, guinea-pig and mouse. 1) Intravenous administration of IP (0.1 approximately 1 mg/kg) exhibited a continuous fall in blood pressure, an increase in heart rate and an increase in cardiac contractile force in the dog. The depressor and chronotropic effects of IP appeared likewise in the pithed dog, and the depressor responses were slightly more evident in the rabbit. The cardiovascular responses to IP were not affected by pretreatment with atropine or diphenhydramine, however, the chronotropic and inotropic effects were completely removed and the depressor response was depressed to some extent by propranolol. On the contrary, a pressor response to adrenaline was reversed to a depressor one after IP in the dog. 2) In heart-lung preparation of dogs, IP brought about slight cardiac stimulating effects, such as an increase in contractile force and a rise in aortic pressure. 3) IP induced a transient slight excitation in in situ movements of the rabbit intestine, and a similar excitation followed with a inhibition in movements of isolated intestine (10(-6), 2.5 X 10(-5) g/ml. This slight excitation was not affected by pretreatment with atropine, whereas the inhibition was depressed to a certain degree by simultaneous pretreatment with phenoxybenzamine and propranolol. IP produced a slight tonic increase in the guinea-pig isolated intestine and inhibited markedly the excitatory effect of histamine in the intestine. 4) IP did not affect the bronchial muscle but inhibited prominently a contractile respose of the muscle to histamine in in situ experiments on guinea-pig. 5) Locomotor activity was reduced dose-dependently and thiopental hypnosis was potentiated similarly after subcutaneous administration of IP (5 approximately 40 mg/kg), while skeletal muscle relaxant effects were not observed. 6) Survival time under a condition of acute anoxia was not changed with a dose of 0.5 and 1 mg/kg, but shortened with a dose of 5 mg/kg. The results suggest that IP has a alpha-blocking, a beta-stimulating and a moderate antihistaminic effects, and shows some cardiovascular effects, such as continuous depressor and chronotropic effects, and a moderate central inhibition.
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