Japanese journal of pharmacology
-
Comparative Study
Anti-inflammatory effect of diclofenac-sodium ointment (cream) in topical application.
This study was performed to develop a topical ointment of diclofenac-Na which has a potent anti-inflammatory activity by oral administration. At first, research was carried out on the ointment base which influences the external anti-inflammatory effect of the drug. Ointments of diclofenac-Na were prepared with three kinds of bases: lipophilic, emulsion (cream) and gel bases; and their anti-inflammatory effects were compared. ⋯ In pain to pressure stimulation, an analgesic effect was observed in the early stage of DF cream application, and its activity was slightly stronger than that of the other ointments. These results show that DF cream has an obvious anti-inflammatory effect as an external preparation, and the activity is comparable or superior to that of similar existing anti-inflammatory ointments. This cream may be considered as useful in the clinical field as a topical anti-inflammatory preparation.
-
Comparative Study
Comparison of the chronotropic responses to local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) of the canine sinus node in situ.
Effects of local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) on the sinus node of the nerve-intact dog heart were studied in situ by means of selective perfusion of the sinus node through the sinus node artery. The agents caused a dose-dependent decrease in heart rate and the order of their potency in decreasing the heart rate was as follows, bupivacaine greater than lidocaine=mepivacaine=prilocaine greater than procaine. ⋯ Tetrodotoxin also prevented the positive chronotropic effect of procaine. From these results the following conclusion can be drawn: the negative chronotropic effects of these agents are induced mainly by a direct inhibitory action on the sinus node, and partly by blockade of sympathetic tone, and the interaction with the postganglionic adrenergic nerves plays an important role in the induction of the positive chronotropic responses to procaine and prilocaine.
-
Comparative Study
Effect of clonidine on blood pressure, heart rate and body temperature in conscious rats.
Effects of clonidine on blood pressure, heart rate and rectal temperature in conscious rats were examined. Clonidine (0.1-1 mg/kg s.c.) caused a prevailing pressor response and dose-dependently a fall in heart rate and body temperature. The pressor response to clonidine (0.3 mg/kg s.c.) was completely reduced by phentolamine (10 mg/kg s.c.), chlorpromazine (10 mg/kg s.c.) but not by hexamethonium (30 mg/kg i.p.), guanethidine (30 mg/kg s.c.) or reserpine (5 mg/kg s.c. 18 hr + mg/kg i.p. 4 hr prior to clonidine). ⋯ The bradycardia with clonidine (0.3 mg/kg s.c.) was significanlty reduced by phentolamine, chlorpromazine or atropine (5 mg/kg s.c.) but was potentiated by reserpine. The hypothermia with clonidine (0.3 mg/kg s.c.) was not influenced by phentolamine or atropine but was significanlty potentiated by chlorpromazine. From the above results it is suggested that the prevailing pressor response to clonidine in conscious rats is due to a stimulation of peripheral alpha-adrenoceptors, the bradycardia with clonidine is exerted through the sympathetic pathway and the baroceptor-vagal reflex, and that the hypothermia with clonidine is mainly due to the central mechanism.
-
A possible mode of cardiovascular actions of dopamine was studied using ephedrine. In the dog pretreated with repeated administrations of ephedrine (total dose, 40 or 80 mg/kg, i.v.) or with combined administrations of ephedrine (total dose, 90 mg/kg, s.c. and i.v.) and reserpine (2 mg/kg, s.c., 24 hr previously), pressor responses to dopamine were eliminated and reversed to depressor responses whereas depressor responses to dopamine were potentiated. Positive chronotropic effects of dopamine were almost eliminated. ⋯ Those of dopamine were not visibly altered, but depressor, negative chronotropic and inotropic effects of dopamine appeared at small doses. In the ephedrine-pretreated dogs, these sympathomimetic effects of dopamine and tyramine after cocaine were strongly depressed and those of noradrenaline were inhibited to a certain degree. The results obtained with ephedrine suggest that dopamine differs from other catecholamines and tyramine in the mode of cardiovascular actions.
-
The pressor response to the intracisternal (i.c.) injection of carbachol (1 mug) in anesthetized rats was analyzed. This response was significantly reduced by the intravenous (i.v.) injection of guanethidine (5 mg), hexamethonium (10 mg) or phentolamine (5 mg), and conversely, potentiated by i.v. desmethylimipramine (0.3 mg), while propranolol (0.5 mg) i.v. selectively inhibited the enlargement of pulse pressure and the tachycardia following i.c. carbachol (1 mug). ⋯ The pressor response to i.c. carbachol (1 mug) remained unchanged after sectioning of the bilateral cervical vagal nerves but disappeared after sectioning of the spinal cord (C7-C8). From the above result it is suggested that the pressor response to i.c. carbachol ortral and peripheral adrenergic mechanisms, and that the sympathetic trunk is the main pathway.