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Biomedical subjects

W C Bowman

Publications and source records attributed to W C Bowman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effects of a new neuromuscular blocking agent (Org 9426) in anaesthetized cats and pigs and in isolated nerve-muscle preparations.

The effects of Org 9426 (the 2-morpholino, 3-hydroxy, 16N-allyl pyrrolidino analogue of vecuronium) were studied in anaesthetized cats and pigs and in isolated nerve--muscle preparations using tension and intracellular recording techniques. In isolated preparations, the effects of Org 9426 were antagonized by neostigmine. No contracture of the chick muscle preparation occurred. Org 9426 reduced the amplitude of endplate currents (EPC) in rat and snake muscle, but had no major effects on EPC decay characteristics, indicating a lack of endplate channel blocking action. In anaesthetized animals, no fasciculations were observed and the neuromuscular block was associated with tetanic and train-of-four fade and was antagonized by neostigmine. In anaesthetized cats and pigs, Org 9426 was approximately 20% as potent as vecuronium, its onset of action was twice as rapid as that of vecuronium in the cat and its duration of action was similar to that of vecuronium in both cats and pigs. It blocked the bradycardia produced by vagal stimulation only in doses greater than those necessary to produce neuromuscular block (ratios 7.2 in the cat and 4.4 in the pig--10-14% of the corresponding ratios for vecuronium). Ganglion block was seen only at doses several times those producing vagal block. In general the effects of Org 9426 on the cardiovascular system were slight, a small depressor effect occurring at high doses in the cat. The 17-hydroxy analogue, the potential metabolite of Org 9426, was approximately 20 times less potent than Org 9426 and is thus unlikely to contribute to the neuromuscular block produced by the parent compound.

Action Potentials↗
PubMed1989

A comparison of the neuromuscular blocking and autonomic effects of two new short-acting muscle relaxants with those of succinylcholine in the anesthetized cat and pig.

The actions of two new steroidal nondepolarizing neuromuscular blocking agents, structurally related to vecuronium, have been compared with those of succinylcholine in anesthetized cats and pigs. Both new compounds (Org 7617 and Org 9616) exhibited properties typical of nondepolarizing relaxants in each species. Org 9616 was one-fifth (ED50 cat tibialis 154 micrograms.kg-1) and Org 7617 was one-tenth (ED50 cat tibialis 287 micrograms.kg-1) as potent as vecuronium as a neuromuscular blocking drug. Both compounds produced rapidly developing muscle relaxation in cats that, like that of succinylcholine, was transient in time course (onset/duration of action--tibialis anterior muscle: Org 7617 1.6/3.9 min; Org 9616 1.5/4.3 min; succinylcholine 1.7/5.7 min). In pigs that were used as a predictor of duration of action in humans, both Org 7617 and Org 9616 also produced short-lived neuromuscular blockade. The neuromuscular blocks produced by Org 7617 and Org 9616 were readily reversed by neostigmine. Both compounds blocked the heart rate responses to vagal stimulation at doses higher than those required to produce neuromuscular block. The vagal:neuromuscular blocking ratio for Org 7617 was 10, and for Org 9616 was 17. These compare to approximate published values for vecuronium, atracurium, and pancuronium of 60, 25, and 3, respectively. Ganglion block was only seen at 30-60 times the neuromuscular blocking doses. Both compounds produced a decrease in arterial blood pressure. This was more pronounced with Org 7617. In addition, Org 9616 produced a slight increase in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1988

Effects of tubocurarine on end-plate current rundown and quantal content during rapid nerve stimulation in the snake.

1. The effects of tubocurarine, pancuronium, vecuronium and trimethyl-tubocurarine were examined on the amplitudes of end-plate currents (EPC) produced by repetitive nerve stimulation in cut voltage-clamped fibres of the costocutaneous muscle of the garter snake. The effects of tubocurarine were further studied on the amplitudes of miniature end-plate currents (MEPC) recorded immediately before the trains of nerve stimulation, thus allowing estimates to be made of EPC quantal content. 2. All four compounds increased the decline of EPC amplitude with successive impulses (rundown), compared with that observed in control end-plates. There was little effect on the decay time constants of EPC and the effects on rundown were not dependent on membrane potential, indicating that end-plate ion channel blockade was not a major effect in producing rundown. 3. In the presence of tubocurarine the quantal content of the EPC in the plateau phase of the trains was reduced when compared with control, indicating a reduction of transmitter mobilization. However tubocurarine had no significant effect on the quantal content of the first EPC of the trains, indicating that the decreased mobilization is not due to an initial effect on transmitter release. 4. It is suggested that the prejunctional effect of tubocurarine which results in increased EPC train rundown is primarily on transmitter mobilization. It is also suggested that the actions of tubocurarine and the other neuromuscular blockers tested are mediated through a prejunctional nicotinic receptor which may act as a positive feedback mechanism modulating transmitter mobilization.

Animals↗
PubMed1988

Structure:action relationships among some desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat.

The hypothesis that the neuromuscular blocking potency of pancuronium and vecuronium depends on the two acetylcholine moieties present at positions 3 and 17 was tested in cats by examining the neuromuscular profile of several desacetoxy analogues. Blockade of sciatic nerve-induced contraction of the tibialis and soleus muscles, as well as the effects on vagal-induced bradycardia and on sympathetically induced contractions of the nictitating membrane, were studied. The bis-desacetoxy analogue of pancuronium (ORG 7931) was one-fifth as potent as the parent compound as a neuromuscular blocking drug and as a vagolytic agent, but the neuromuscular block was faster in onset and shorter in duration than that produced by pancuronium. The desacetoxy analogues of vecuronium (ORG 8730 and ORG 8764) also were less potent neuromuscular blocking drugs, and, in addition, produced more vagal block than did vecuronium itself. The neuromuscular block produced by these desacetoxy analogues was of more rapid onset and shorter duration than that produced by vecuronium. The results thus showed that the greater neuromuscular blocking potency of pancuronium and vecuronium is lost after removal of one or both of the acetylcholine moieties. An analysis of the relationship between neuromuscular blocking dose and duration of action revealed that it was reciprocal, and it is suggested that a nondepolarizing equivalent of suxamethonium, when discovered, may necessarily be a drug of relatively low potency.

Animals↗
PubMed1985

Cyclic nucleotides and contractility of isolated soleus muscle.

The effects of isoprenaline, terbutaline and forskolin were examined on cyclic nucleotide concentrations and contractile responses in guinea-pig isolated soleus muscles. Isoprenaline and terbutaline induced rapid, concentration-related reductions in the tension and degree of fusion of subtetanic contractions of the soleus muscle. These changes were associated with increases (about 2 fold) in the levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the muscle cells. Propranolol competitively inhibited these responses. Forskolin failed to elicit a sympathomimetic response in the soleus muscles despite increasing (by about 20 fold) the intracellular concentration of cyclic AMP. Forskolin also failed to potentiate the effects induced by isoprenaline. The levels of cyclic GMP in the soleus were increased by isoprenaline (about 1.5 fold) and forskolin (about 2.5 fold). Terbutaline was without effect on cyclic GMP levels. These data suggest either that cyclic AMP is not involved as the mediator underlying beta-adrenoceptor-induced changes in contractility of slow contracting skeletal muscles or that forskolin does not stimulate the particular adenylate cyclase that leads to appropriate increases in cyclic AMP in those functional compartments associated with modulation of intracellular Ca2+ movements. Cyclic GMP is not involved in modifying changes in contractility of the soleus muscle.

Animals↗
PubMed1982

Some actions of Org NC 45 and of edrophonium in the anaesthetized cat and in man.

Some actions of the muscle relaxant drug Org NC 45 on the tibialis anterior muscle of cats under barbiturate-chloralose anaesthesia have been studied. Its effects were characteristic of a neuromuscular blocking agent that acts predominantly, although not necessarily exclusively, by blocking postjunctional cholinoceptors. It was confirmed that one of the important features of the action of Org NC 45 is that, despite its high potency, its offset of action is unusually rapid. The pronounced antagonism of the block following an interposed tetanus suggested that Org NC 45 is more easily displaced from the endplate cholinoceptors than are tubocurarine or pancuronium, and this led to the idea, confirmed by experiment, that edrophonium would be a more effective antagonist of Org NC 45 than of most other neuromuscular blocking drugs. Edrophonium was about 12 times less potent than neostigmine in antagonizing Org NC 45. However, with equipotent antagonistic doses, edrophonium restored transmission to control (as measured by the train-of-four test) at least twice as rapidly as neostigmine and, more importantly, edrophonium had a much weaker effect than neostigmine on the cardiac vagus. The results obtained in cats with edrophonium were essentially confirmed in preliminary studies on nine anaesthesized patients. In these studies, a dose of edrophonium 0.5 mg kg-1 i.v. was found to produce adequate and rapid antagonism of Org NC 45, and because of the relatively weak side-effects of edrophonium, it was necessary, about 30 s before edrophonium, to administer only 0.6 mg of atropine (about 9 micrograms kg-1), which is half the dose commonly used when neostigmine is the reversal agent. These preliminary observations in man suggest that edrophonium may be the reversal agent of choice for Org NC 45.

Adult↗
PubMed1981

Actions of 4-aminopyridine on the cardiovascular systems of anaesthetized cats and dogs.

The effects of the anti-curare agent 4-aminopyridine on the cardiovascular systems of cats and greyhounds under barbiturate-chloralose anaesthesia have been studied. In both species, 4-amino-pyridine produced a transient atropine-sensitive decrease in arterial pressure followed by a prolonged adrenergically-mediated increase. In the cat, the cardiac responses to vagal stimulation and nictitating membrane responses to sympathetic stimulation were augmented after injection of 4-aminopyridine, and the evidence indicated that these effects were the results of increased release of neurotransmitters. In the greyhound, 4-aminopyridine produced increases in the left ventricular systolic pressure and dP/dt max, right atrial pressure, stroke volume, myocardial blood flow, myocardial oxygen consumption, external cardiac work, arterial oxygen content and blood haemoglobin. These effects were attributable to facilitation of sympathetic transmission to the blood vessels, heart and spleen. Heart rate was not much affected because facilitation of vagal transmission to the S-A node counteracted the increased sympathetic effect. In the greyhound, 4-aminopyridine also produced temporary cardiac arrhythmia which was only partly attributable to facilitated sympathetic transmission. In addition there was evidence of a central stimulant action of 4-aminopyridine and of a stimulant action on visceral activity. It is concluded that, while 4-aminopyridine may be useful in certain relatively rare conditions of neuromuscular transmission failure, its actions are too widespread for routine use as an antagonist to non-depolarizing neuromuscular blocking drugs.

4-Aminopyridine↗
PubMed1981

Awareness of potential drug interactions with anticoagulants.

A survey by questionnaire returned by 180 individuals determined the awareness of doctors and medical students and pharmacists and undergraduate pharmacy students to the potential of drug interactions occurring in patients receiving anticoagulant drugs. Pharmacy students and hospital pharmacists were particularly well informed of the hazards of drug interactions; community pharmacists were less well informed. Hospital medical consultants, registrars and general practitioners were more aware of the hazards of interactions than medical students. The survey clearly shows the need for more education of doctors and pharmacists on drug interactions, especially those involving anticoagulant drugs.

Anticoagulants↗
PubMed1977

The actions of aminopyridines on avian muscle.

The effects of 2-, 3-, and 4-aminopyridines were investigated on the isolated chick biventer cervicis nerve-muscle preparation and on nerve-free cell cultures of embryonic chick skeletal muscle. All 3 compounds reversed tubocurarine blockade and augmented twitch height in indirectly stimulated biventer cervicis preparations. 4-Aminopyridine was approximately 10 times more potent than 2-, or 3-aminopyridine. Twitch augmentation was also seen in directly stimulated preparations but to a much lesser extent. The compounds did not have significant anticholinesterase activity, nor did they have any depolarizing activity when tested on nerve-free cultured muscle fibres. At high concentrations the aminopyridines produced a maintained contracture in the biventer preparations which was enhanced by neostigmine and inhibited by tubocurarine. It is suggested that the aminopyridines facilitate neuromuscular transmission by increasing acetylcholine release in response to nerve stimulation, and that the compounds can also increase spontaneous transmitter release.

Acetylcholine↗