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Biomedical subjects

C Raper

Publications and source records attributed to C Raper.

At least 73 records · Page 4Linked to original sources
PubMed1968

Some studies on peripheral actions of mephenesin, methocarbamol and diazepam.

1. Mephenesin, methocarbamol and diazepam abolished polysynaptic reflex contractions of the cat tibialis anterior muscle elicited by stimulation of the homolateral femoral nerve.2. Mephenesin and methocarbamol caused a prolongation of the mean refractory period of directly or indirectly stimulated skeletal muscle. These effects were due to a direct action on the muscle fibres. There was no effect on responses to single stimuli.3. The increase in refractory period produced by mephenesin was greater in indirectly than in directly stimulated rat diaphragms. Experiments using the isolated phrenic nerve suggest that this difference is due to the local anaesthetic action of mephenesin.4. In the indirectly stimulated cat tibialis anterior muscle high frequency stimulation resulted in a non-maintained tetanus in the presence of mephenesin and methocarbamol.5. Diazepam was without peripheral effects on the responses of skeletal muscle.6. The results with mephenesin and methocarbamol are discussed in relation to their mode of action in reducing muscle spasm.

Action Potentials↗
PubMedDate not supplied

Effects of some catecholamines on the cat cardiovascular system: interactions with adrenoceptor antagonists.

The effects of intravenous infusions of norepinephrine, epinephrine, isoproterenol, N-t-butylnorepinephrine, oxymethyleneisoproterenol, and RO363 on heart rate, mean arterial blood pressure, cardiac output, total peripheral resistance, and stroke volume were evaluated in chloralose-anaesthetized cats before and after phentolamine, propranolol, atenolol, and butoxamine. Pressor responses to both norepinephrine and epinephrine largely resulted from alpha-receptor-mediated increases in total peripheral resistance. Vasomotor reversal was noted with both drugs in the presence of alpha-receptor blockade. Dilator responses to norepinephrine were abolished by the beta 1-receptor selective antagonist atenolol, as were those to the beta 1-receptor selective agonists oxymethyleneisoproterenol and RO363. Dilator responses to epinephrine were abolished by the beta 2-receptor selective antagonist butoxamine, as were those to N-t-butylnorepinephrine (beta 2-selective) and isoproterenol (nonselective). These results indicate that in addition to beta 2-receptors, beta 1-receptors subserving vasodilatation occur in the cat vasculature. Atenolol displayed agonist-dependent inhibition of the cardiac responses. Responses to noradrenaline, RO363, and oxymethyleneisoproterenol were blocked to a greater extent than were those to epinephrine, N-t-butylnorepinephrine, and isoproterenol. Butoxamine did not display any marked agonist-dependent inhibition of cardiac responses. Nevertheless, the results are in accord with previous suggestions that cardiostimulant beta 2-receptors exist in the cat heart. Interpretation of the actions of catecholamines may be complicated by mixed beta-adrenoceptor populations in the cat cardiovascular system.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Cardiovascular actions of xamoterol (ICI 118,587) in anaesthetized cats, rats, and guinea pigs.

The maximal increases in heart rate produced by intravenous xamoterol in anaesthetized cats and rats are less than that of (-)-isoprenaline. In cats, blood pressure was slightly raised, while in rats, supramaximal cardiac-stimulant doses produced reductions in blood pressure. In anaesthetized guinea pigs, cardiac-stimulant effects of xamoterol were evident only after treatment with hexamethonium. In all three species cardiovascular responses to xamoterol were antagonized by beta-adrenoceptor antagonists. Thus, xamoterol is a partial agonist which displays beta 1-adrenoceptor selectivity. In cats, infusions of xamoterol elicited beta-adrenoceptor-mediated increases in heart rate, blood pressure, and cardiac output, while calculated total peripheral resistance was little affected and, unexpectedly, stroke volume was reduced. These cardiovascular effects were unaffected by hexamethonium or captopril. Both xamoterol and (-)-isoprenaline elevated left ventricular dP/dtmax and reduced central venous pressure. When cat heart rate was paced over a range (175-250 beats/min) corresponding to the beta-receptor-mediated chronotropic effects, an inverse relationship between rate and stroke volume was observed. The rate-induced reduction in stroke volume offers the best explanation for the decrease in stroke volume produced by xamoterol. In general, the effects of beta-adrenoceptor agonists on stroke volume in the anaesthetized cat appear to represent a balance between a rate-related reduction and a drug-induced elevation of this parameter.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Influence of changes in amine substitution on the beta-adrenoceptor stimulant activity of soterenol and related compounds in the anaesthetized cat.

1. Three 3-methanesulphonamido, 4-hydroxy ring substituted phenylethanolamines with N-isopropyl (soterenol), N-t-butyl (MJ7999-1) and N-(1-phenyl-t-butyl)(MJ9184-1) amine substituents have been compared with ()-isoprenaline for their ability to produce beta-receptor mediated reductions in serotonin-induced increases in pulmonary resistance, decreases in soleus muscle contractility, and increases in heart rate in anaesthetized cats. For each parameter, the dose of a compound required to produce 50% of its maximal response (ED50) was calculated. 2. For all three parameters ()-isoprenaline was the most potent of the compounds studied, and the rank order of potency of the methanesulphonanilides was MJ9184-1 (N-(1-phenyl-t-butyl))congruent to MJ7999-1 (N-t-butyl) greater than soterenol (N-isopropyl). 3. For each individual drug, molar dose-ratios [drug:()-isoprenaline] were calculated. Ratios for the effects of the compounds on the soleus muscle and in the bronchi were similar. With each compound higher dose-ratios were found in the heart. The rank order for relative beta2-selectivity was soterenol (N-isopropyl) greater than MJ7999-1 (N-t-butyl) congruent to MJ9184-1 (N-(1-phenyl-t-butyl)).

Adrenergic beta-Agonists↗
PubMedDate not supplied

Beta-adrenoreceptors in denervated skeletal muscles of the cat.

1. A number of sympathomimetic amines have been compared with (-)-isoprenaline for their ability to produce contractions in chronically denervated soleus and tibialis anterior muscles and to increase heart rate in bilaterally vagotomized anaesthetized cats. 2. The mean dose-ratios ((-)-isoprenaline equals 1) for adrenaline, orciprenaline and salbutamol were 2.9, 29.7 and 11.5 respectively in the tibialis anterior muscle and 3.5, 24.1 and 14.3 in the soleus muscle. The dose-ratios for noradrenaline were 21.1 in the tibialis anterior and 57.6 in the soleus muscle. 3. The dose-ratios ((-)-isoprenaline equals 1) obtained for the positive chronotropic effects of the drugs in bilaterally vagotomized cats were 14.5, 14.6, 29.6 and 24.2 for adrenaline, noradrenaline, orciprenaline and salbutamol respectively. 4. The beta2-receptor antagonists butoxamine and H35/25 antagonized the vasodepressor and skeletal muscle responses to (-)-isoprenaline to a greater extent than the cardiac responses, whereas the beta1-receptor selective antagonists practolol and H93/26 antagonized cardiac to a greater extent than vascular and skeletal muscle responses. 5. The results obtained suggest that the contractions of denervated skeletal muscle to sympathomimetic drugs result from stimulation of beta2-adrenoreceptors.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Comparison of the effects of (--)-isoprenaline, orciprenaline terbutaline, and Me506 on heart rate, soleus muscle contractility and pulmonary resistance of anaesthetized cats.

1. Three resorcinol derivatives with N-isopropyl (orciprenaline), N-t-butyl (terbutaline) and N-p-hydroxypheny-t-butyl (Me506) amine substituents have been compared with (--)-isoprenaline for their ability to produce beta-receptor mediated reductions in serotonin-induced increases in pulmonary resistance, decreases in soleus muscle contractility and increases in heart rate in anaesthetized cats. 2. For all parameters studied the four compounds produced similar maximal responses and dose-response curves were close to parallel. From the graphs doses of the compounds producing 50% of the maximal response (ED50) were interpolated, and from these dose-ratios with respect to (--)-isoprenaline [drug ED50:(--)-isoprenaline ED50] were calculated on a molar basis. 3. Increasing the size of the amine substituent from N-isopropyl to N-t-butyl led to an increase in beta-receptor stimulant activity in bronchial and skeletal muscle, but not in the heart. The change from N-t-butyl to N-p-hydroxyphenyl-t-butyl did not further affect stimulant activity in any of the parameters studied. 4. Calculation of selectivity ratios [molar dose-ratio (heart): molar dose-ratio (pulmonary resistance)] showed that orciprenaline was non-selective, and that terbutaline and Me506 showed a similar degree of selectivity for beta2- as opposed to beta1-receptor mediated actions.

Airway Resistance↗
PubMedDate not supplied

Species difference in the beta1/beta2-adrenoceptor selectivity of SM220CL in the cat and guinea-pig.

The beta-receptor stimulant effects of Sm220Cl, dl-N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (beta1) and tracheal (beta2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability to increase the heart rate (beta1), reduce serotonin-induced increases in pulmonary resistance (beta2), and decrease soleus muscle contractility (beta2) in vivo in the two species. 3. In all experiments cumulative concentration or dose-effect curves were established, EC50 or ED50 values obtained and molar activity-ratios (Sm220Cl: (-)-isoprenaline) calculated. 4. Calculated selectivity ratios [activity-ratio (heart):activity-ratio (bronchial smooth muscle)] from the in vitro experiments showed that Sm220Cl possessed beta2-receptor selectivity. This was more marked in guinea-pig than in cat preparations. 5. In the anaesthetized animals this species difference was more apparent; in cats Sm220Cl was non-selective in its actions for beta1- and beta2-receptor mediated responses, while marked beta2-receptor selectivity was obtained in the guinea-pig. 6. Since in both species the activity-ratios for beta2-receptor mediated actions are similar, the differences in the beta1/beta2-receptor selectivity of Sm220Cl are caused by the divergent cardiac effects produced by the drug.

Airway Resistance↗
PubMedDate not supplied

Agonistic and antagonistic actions of 3,4-dihydroxy-substituted phenoxypropanolamines in guinea-pig atria and trachea.

1. Racemic mixtures of noradrenaline, adrenaline, isoprenaline, N-t-butylnor-adrenaline and their corresponding derivatives containing an oxymethylene (OM) link between the phenyl ring and ethanolamine side-chain have been tested for their effects on beta-adrenoceptors in isolated guinea-pig atrial and tracheal preparations. 2. In atrial and in spontaneously contracted tracheal preparations both the parent catecholamines and their corresponding OM-derivatives had a similar order of potency as beta-receptor agonists. 3. In carbachol-stimulated tracheal preparations the OM-derivatives were shown to have partial agonistic actions. 4. As in other phenylethanolamines and phenoxypropanolamines, both the agonistic and antagonistic potency of the OM-derivatives increased with increasing amine substitution.

Airway Resistance↗
PubMedDate not supplied

Comparison of the beta-adrenoceptor effects of soterenol and its 3-hydroxy, 4-sulphonamido isomer (MJ6987-1) in isolated tissues from the guninea-pig.

1. Soterenol and its 3-hydroxy, 4-methanesulphonamido isomer (MJ6987-1) were compared with isoprenaline for beta-adrenoceptor mediated effects in guinea-pig atrial, tracheal, uterine and ileal preparations. In addition, MJ6987-1 was tested for its effects in the atria of cats, rabbits and rats. 2. Soterenol had a lower intrinsic activity and was approximately two to six times less active than isoprenaline in all preparations. 3. MJ6987-1 was a full agonist, being some 30--200 times less active than isoprenaline at beta 1-receptor sites and greater than 3000 times less active in preparations where beta 2-receptor activation was involved. 4. Change in the position of the ring substituents in soterenol leads to the production of beta 1-receptor selective agonist.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Leakage of catecholamines from rabbit cerebrospinal fluid following intracerebroventricular injection.

The intracerebroventricular (i.c.v.) injection of (-)-isoprenaline and the selective beta 1-adrenoceptor agonist, RO363, elicited reproducible dose-related increases in heart rate in unanaesthetized and anaesthetized rabbits. (-)-Isoprenaline produced vasodepressor effects in unanaesthetized animals, whereas both catecholamines decreased blood pressure in anaesthetized rabbits. Pretreatment with guanethidine sulphate (5 mg/kg i.v.) reduced but did not abolish the tachycardia elicited by i.c.v. RO363, whereas heart rate responses to i.c.v. (-)-isoprenaline were unaffected. Pretreatment of anaesthetized rabbits with hexamethonium bromide (10 mg/kg i.v.) did not markedly affect the tachycardia elicited by i.c.v. RO363 and reduced the response to i.c.v. (-)-isoprenaline in only one out of five experiments. The results suggest that there is a marked leakage of centrally administered catecholamines into the peripheral circulation and that the rabbit may be unsuited for examining centrally mediated cardiovascular effects of catecholamines.

Adrenergic beta-Agonists↗