General pharmacology of a Pseudomonas vaccine prepared from outer-membrane fractions of Pseudomonas aeruginosa.

CFC-101 is a novel Pseudomonas vaccine with high effectiveness against Pseudomonas infection and is currently under clinical evaluation. The general pharmacological properties of this vaccine were evaluated in mice, rats, guinea pig ileum, and dogs. In vivo doses of 0.

[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium].

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.

Analgesic activity of the lysozyme peptide N-(N-L-threonyl-L-alpha-aspartyl)-L-tyrosine in the monkey and the dog.

N-(N-L-Threonyl-L-alpha-aspartyl)-L-tyrosine (CAS 115053-54-8, SPA-S-646) was originally derived from lysozyme. It has previously been found to have analgesic properties following oral and intravenous administration to laboratory rodents. In the rhesus monkey, intramuscular administration of SPA-S-646 caused a dose-related analgesia.

General pharmacology of [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3- dihydro-1H-pyrrolizine-5-yl]-acetic acid in experimental animals.

[2,2-Dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]-acetic acid (ML 3000) is a newly synthesized compound with analgesic, antipyretic and anti-inflammatory activity. The general pharmacological effects of ML 3000 following oral administration were investigated in experimental animals. The results showed that with regard to the CNS, ML 3000 did not affect behaviour in the Irwin test, locomotor activity or hexobarbital-induced sleep at doses of 30, 100 and 300 mg/kg.

Acute and chronic anti-inflammatory properties of [2,2-dimethyl-6-(4- chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid.

The carrageenan-induced paw oedema in the rat was chosen as the experimental model for acute antiphlogistic activity. ED50 values of 3 mg/kg p.o.

Gastrointestinal tolerance of [2,2-dimethyl-6-(4-chlorophenyl-7-phenyl- 2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid in the rat.

The gastrointestinal tolerance of [2,2-dimethyl-6-(4-chlorophenyl)-7- phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid (ML 3000, CAS 156897-06-2) has been tested in comparison with indometacin, after both single and multiple administrations for 5 and 11 days in an in vivo rat assay. A single oral administration of ML 3000 at doses of 10, 30 and 100 mg/kg produced no gastrointestinal damage. Repeated oral administration of ML 3000 at daily doses of 10, 30 and 100 mg/kg produced slight gastrointestinal damage, but the effect was minimal and was not found to be statistically significant.

Antitussive effects of levodropropizine in the dog.

The antitussive activity of levodropropizine (S(-)3-(4-phenyl-piperazine-1-yl)-propane-1,2-diol, DF 526, CAS 99291-25-5) was evaluated after oral administration to the conscious dog. Levodropropizine had a good antitussive activity, comparable with, but having a longer duration of action than dropropizine, the racemate from which it is derived. The antitussive activity of levodropropizine in the dog was approximately 1/20 of that of codeine phosphate.

Pharmacological effects of cefclidin on the central nervous system.

The effects of cefclidin (CFCL), a novel antibacterial agent, on the central nervous system (CNS) were examined in a variety of animal models. The effects of cefazolin (CEZ) were also examined for comparative purposes. In the animal models used CFCL whilst having some effects at the doses examined, failed to show an overall consistent effect on the CNS.

Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation.

The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v.

Antitussive action of the new anilide derivative vadocaine hydrochloride compared with codeine phosphate in four animal models.

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) is a novel antitussive compound structurally resembling local anaesthetics. Its antitussive profile was studied in several animal models. In guinea-pigs, vadocaine reduced by about 70% the cough episodes induced by sulphur dioxide or ammonia.

The physical dependence liabilities of oxybutynin and morphine in rats.

The anticholinergic/antispasmodic agent oxybutynin does not induce physical dependence in rats when administered by oral gavage twice daily for 40 days; nor did challenge with naloxone precipitate withdrawal signs in these (oxybutynin-treated) animals. In contrast, morphine treatment resulted in a high degree of physical dependence as evidenced by the withdrawal signs noted after treatment was halted. Challenge with naloxone also induced severe withdrawal signs in morphine-treated rats.

Study of the effects of oral administration of CDP-choline on EEG changes and lethality induced by epidural compression in the anaesthetised cat.

The effects of repeated oral administration of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) and vehicle on the EEG changes induced by epidural brain compression have been studied in the anaesthetised cat. The effects on arterial pressure and heart rate were also monitored. CDP-Choline-treated cats exhibited a statistically significant increase in resistance to the effects of mechanical compression of the brain when compared with the vehicle-treated group.

Cardioregulatory properties of indoramin in the rat.

The antihypertensive action of the competitive alpha-adrenoceptor antagonist indoramin is not accompanied by reflex tachycardia in animals or man. The possibility that the established local anaesthetic property of indoramin is involved in its cardioinhibitory action has been investigated. Indoramin evoked a dose-dependent bradycardia in anaesthetized/pithed rats.

Hypertension: its effect on the stimulated release of dopamine-beta-hydroxylase in the rat.

Plasma dopamine-beta-hydroxylase (DBH) concentrations have been postulated as providing an index of sympathetic nerve activity. Using a microspectrophotometric assay system, plasma DBH concentrations have been measured in emergent blood from autoperfused heart, spleen and mesentery of normotensive, deoxycorticosterone (doca)/NaCl-treated, Goldblatt (1 kidney) renal and spontaneously hypertensive rats following sympathetic nerve outflow stimulation. Changes in plasma DBH concentrations as a result of sympathetic nerve outflow stimulation rates of 1--25 Hz for the mesentery and spleen and 1--4 Hz for the heart, were found to be frequency-dependent in all groups.

Dopamine-beta-hydroxylase release following acute selective sympathetic nerve stimulation of the heart, spleen and mesentery.

In increase in the concentration of dopamine-beta-hydroxylase (DBH) in the blood perfusates of the heart, spleen and mesentery of pithed rats was detected following selective sympathetic nerve stimulation. Furthermore, the concentration of enzyme released by each organ correlated with the stimulation frequency. The results provide further corroborative evidence that the concentration of DBH in the plasma is related to the degree of sympathetic tone.