In vitro and in vivo evaluation of the anti-asthmatic activities of fractions from Pheretima.

Pheretima (family Megascolecidae) has been documented as a potent agent for the treatment of cough and breathing difficulty in traditional Chinese medicine for nearly 2000 years. The water extract of Pheretima was separated into three fractions of the ethanolic precipitate, the alkaline fraction and the acidic fraction. Among the three fractions, the acidic fraction showed the most potent spasmolytic effects on histamine-induced contractions in isolated guinea pig tracheal rings, and the most inhibitory activities on increase of short circuit current induced by carbachol in isolated rat tracheal epitheliums with the IC50 values of 0.15 and 0.08 mg/ml, respectively. Further in vivo studies also displayed that the acidic fraction could protect experimental asthma model induced by the combination of histamine and acetylcholine chloride in guinea pigs to prolong the latent periods of asthma (P < 0.05) and significantly decrease the cough frequency caused by ammonia water in mice (P < 0.001).

Pancuronium masks the prejunctional muscarinic autoreceptor in guinea pig tracheal smooth muscle.

The effect of pancuronium pretreatment on the function of the prejunctional muscarinic receptor in guinea-pig trachea was studied by using electrical field stimulation (EFS). The effects of cumulative doses of the muscarinic M2 receptor antagonist gallamine were investigated in tracheal smooth muscle strips from guinea-pigs after addition of pancuronium in vitro and in strips from guinea-pigs which had been pretreated with doses of pancuronium that caused 100% neuromuscular blockade. The results of both types of experiments were compared to those of control groups of the same size. In all strips a dose response curve with cumulative doses of methacholine was made before EFS was switched on. No differences were found between the mean pD2 value and slope of the concentration-response curves of untreated guinea-pigs and animals treated with anaesthetics and pancuronium. The animals showed variable responses to pancuronium. The bath concentration of pancuronium which decreased the EFS-induced contraction to half the original value varied between 14-61 microM. The intravenous dose necessary to paralyze the muscles, varied among the different guinea-pigs from 0.017-0.085 mg.kg-1. The EFS-induced contraction for the concentration range of gallamine 0.32 microM-0.32 mM was found to differ significantly between the strips treated with pancuronium in the organ bath and their control group. For the guinea-pigs anaesthetized and pretreated with pancuronium a significant difference with control was observed at gallamine concentrations ranging from 0.032-0.32 mM. These results show that pancuronium, added to the organ bath as well as administered intravenously to the guinea-pig, masked the inhibitory muscarinic receptor.

[Studies on antitussive, antiasthmatic and expectorant action of chenodeoxycholine acid].

OBJECTIVE: In this paper, antitussive, antiasthmatic and expectorant action of chenodeoxycholine acid (CDCA) were studied. METHOD: The method of strong aqua ammoniae induced cough and sulfur dioxide induced cough, the method of tracheal volume and tracheal spiral line, and phenolsulfonphthalein excretion test. RESULTS: CDCA was able to prolong cough latent period and decrease cough rate significantly in mice resulted from strong aqua ammoniae and sulfur doxide, and inhibit contraction of whole-body or extracorpored tracheal smooth muscle in guinea pig resulted from histamine phosphate. Besides, CDCA can increase phenolsulfonphthalein excretion quantity of trachea in mice, singnificantly. CONCLUSION: CDCA has antitussive, antiasthmatic, expectorant actions.

Comparative haemodynamic alterations induced by pipecuronium and pancuronium.

Haemodynamic effects of pipecuronium bromide (Pi.) and pancuronium bromide (Pa.) were studied on isolated rabbit's heart, guinea pig's tracheal chain as well as the blood pressure in pentobarbital anaesthetized dogs. Pi. induced negative inotropic and chronotropic effects on the isolated rabbit's heart especially in lower concentrations. However, higher concentrations provoked two opposite effects, negative chronotropic and positive inotropic activity. In addition, Pa. in lower concentrations caused positive inotropic and negative chronotropic activity, while higher concentrations induced negative inotropic and chronotropic activity. Cardioinhibitory actions of both tested drugs are not due to either cholinergic or beta 1-adrenergic blocking effect but it may be due to nicotine-like activity. In anaesthetized dogs, i.v. injections of both tested drugs produced a transient decrease in systolic and diastolic pressure in doses above the therapeutic level. This effect may be referred to the partial ganglion blocking effect of both tested drugs.

Pancuronium bromide does not lower airway pressures during intermittent positive pressure ventilation in young cats.

High intrapulmonary pressure is probably an important factor in the development of extra-alveolar air leaks and bronchopulmonary dysplasia during neonatal intermittent positive pressure ventilation (IPPV). Spontaneous breathing, which may be asynchronous with the ventilator as a result of hypoventilation or sometimes of the ventilatory pattern of the ventilator, can be prevented by neuromuscular blockade. During neuromuscular blockade with pancuronium bromide the central inspiratory (phrenic nerve activity) activity could be inhibited during IPPV at all ventilatory frequencies tested, but a lower arterial PCO2 and a higher pH were needed to achieve inhibition at a low frequency (15 bpm). In the present study it was observed that central inspiratory activity in cats was stimulated by intravenous injection of pancuronium bromide. In cats not subjected to neuromuscular blockade the inspiratory activity was inhibited during IPPV at all ventilatory frequencies studied. At the onset of inhibition of this activity, the arterial blood gases and pH in these animals were almost the same at all ventilatory frequencies. When ventilation was administered at a low frequency, higher peak intratracheal pressures were needed to obtain inhibition of central inspiratory activity than when high frequencies were used, both before and after neuromuscular blockade.

Physical, chemical and biological assay of Tylophora indica mother tincture--a comparative study.

Successful use of homeopathic medicines is related to the purity and quality of crude and finished products. To maintain the quality of Tylophora indica mother tincture, a comparative study on physical, chemical and biological assay of five samples (reference laboratory and market) of Tylophora indica was carried out. The market sample showed different chromatographic characteristics and may have been prepared from a different species. T. indica has antispasmodic and hypotensive properties.

Steroidal muscle relaxants attenuate the contractile and phosphatidylinositol responses of rat trachea.

Interaction of the steroidal muscle relaxants, pancuronium, vecuronium and rocuronium with airway muscarinic receptors of rat trachea was investigated in vitro concerning the contractile and phosphatidylinositol (PI) responses. Pancuronium and vecuronium attenuated, while rocuronium did not affect carbachol (CCh)-induced contraction and CCh-induced IP1 accumulation. Pancuronium could inhibit completely CCh-induced contraction at a dose of 30 microM, while it could not inhibit completely CCh-induced IP1 accumulation at the same dose. These drugs attenuated KCl-induced contraction. These results suggest that pancuronium and vecuronium would attenuate airway smooth muscle contraction through the inhibition of muscarinic receptor-mediated PI response, and that the inhibition of voltage-operated Ca++ channel might be involved, in part, in the attenuation by pancuronium of the contraction.