British journal of pharmacology
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1. The cardiovascular and behavioural effects of cholinomimetic drugs injected through a cannula chronically implanted into a lateral cerebral ventricle were examined in unanaesthetized dogs.2. Acetylcholine (ACh) (10-20 mug) produced an increase in arterial pressure and heart rate, the dogs became more alert, moved their heads, licked and swallowed and then became drowsy.3. ⋯ The responses to nicotine were not reproducible if injections were repeated on the same day but could be again produced if a few days were allowed to elapse between injections.7. An increased heart rate occurred during the pressor response to the cholinomimetic drugs but when a comparable pressor response was produced by intravenous infusion of noradrenaline in the same unanaesthetized dogs pronounced reflex bradycardia resulted.8. The results indicate that the activation of both muscarinic and nicotinic cholinergic mechanisms leads to cardiovascular and behavioural effects in the conscious dog although the site of action and peripheral mechanisms have not been determined.
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1. Administration of 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A), 40 mg/kg, i.p., simultaneously or 40 min before sulphacetamide sodium, 100 mg/kg, i.p., was associated with a three-fold increase in sulphacetamide plasma concentration of rats. This effect was no longer evident after 30 minutes.2. ⋯ When sulphacetamide was administered i.v., a similar phenomenon was observed but the differences were less marked.4. Pretreatment with SKF 525-A was associated with decreased excretion of sulphacetamide by the kidney.5. It is concluded that SKF 525-A may alter the distribution and excretion of drugs as well as inhibiting drug metabolizing enzymes.
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1. The anaesthetic, cardiovascular, respiratory and adverse effects produced by the intravenous injection of CT 1341, thiopentone, methohexitone, pentobarbitone, propanidid and ketamine have been compared in unrestrained cats prepared with chronically implanted venous and arterial cannulae. Aortic blood pressure and heart rates were monitored before, during and after loss of consciousness.2. ⋯ Induction was slower after small doses and these produced circulatory stimulation, catatonia and bizarre behavioural effects. Large doses caused respiratory and circulatory depression and recovery was protracted.6. It is concluded that CT 1341 has a wider therapeutic latitude, produces less respiratory depression and has other advantages over the currently used intravenous anaesthetics.
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1. The duration of the effect of a single large dose of hyoscine, in reducing the salivary response of mice to pilocarpine, was established as less than 66 hours.2. Supersensitivity was observed, after daily oral dosing with hyoscine, in the increased salivation of mice in response to pilocarpine injected at least 66 h after withdrawing hyoscine.3. ⋯ The period after withdrawal for which supersensitivity could be detected was 6 days.5. The maximum salivary response to pilocarpine was increased by chronic hyoscine pretreatment.6. The antagonism of a single dose of hyoscine to pilocarpine salivation, as expressed by the dose-ratio of pilocarpine, was not altered by chronic hyoscine pre-treatment.