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  • Title: Investigation into some imidazoline compounds, with respect to peripheral alpha-adrenoceptor stimulation and depression of cardiovascular centers.
    Author: Kobinger W, Pichler L.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1975; 291(2):175-91. PubMed ID: 628.
    Abstract:
    Peripheral alpha-adrenoceptor stimulation was tested by means of hypertensive effects of the drugs following i.v. injection in spinal rats. Naphazoline (NP), oxymetazoline (OM), St 91-2-(2,6-diethylphenylimino)-2-imidazolidine--and St 1697--2-(2-ethyl, 6-methylphenylimino)-2-imidazolidine--were 3 to 5 times more potent in tthis respect thatn clonidine (CLON) whereas St 363--2-(2,4-dichlorophenylimino)-2-imidazolidine--and xylazine (XY) exerted only approx. 1/20 the effect of that of clonidine. Sympathoinhibitory activity after i.v. injection was tested by the bradycardiac effect in vagotomized rats; St 1697, St 363 and XY were active, approx. 1/10-1/30 of CLON, whereas NP, OM and St 91 were inactive. However, following intracisternal (i.ci.) injection of cardiovascular depression, typical for clonidine: (1) in dogs with blocked beta-adrenoceptors, the drugs facilitated the vagally meditated cardiodepressor reflex in response to baroreceptor stimulation by i.v. injection of angiotensin; (2) in dogs treated with atropine and in (3) vagotomized cats (only NP, OM and St 363) a long lasting decrease in heart rate was observed. Some of the experiments were complicated by increases in blood pressure, due to the "leakage" of small amounts of the highly vasopressor active drugs, from the cisternal spaces into the peripheral circulation. The majority of results indicated, that the central cardiovascular depressor effects of the tested drugs depend on their alpha-adrenoreceptor stimulating potency and on their ability to penetrate from cerebrospinal fluid or from the blood to cardiovascular centers. Relationships between the ability for penetration and the lipoid affinity are discussed.
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