British journal of pharmacology
-
1 The potency of a series of short-acting anaesthetics was established by measuring the duration of the loss of righting reflex following a single bolus injection into the tail vein of male Wistar rats. The agents were, in order of potency, etomidate, alphaxalone, methohexitone, alphadalone acetate and propanidid.2 The potency of binary mixtures of these agents was also assessed to see whether the anaesthetic effects of different agents were additive as classical theories of anaesthesia suggest. ⋯ Mixtures of etomidate and methohexitone were not examined.3 Mixtures of alphaxalone and either methohexitone or pentobarbitone produced a greater depression of synaptic transmission in in vitro preparations of guinea-pig olfactory cortex than would have been expected from the sum of the activities of the individual anaesthetics. Other combinations of anaesthetics did not show similar effects although the interaction between alphaxalone and etomidate was not examined.4 Neither alphaxalone nor pentobarbitone affected the membrane: buffer partition coefficient of the other for a model membrane system.5 These results are interpreted as evidence against the classical unitary hypotheses of anaesthetic action based on correlations of anaesthetic potency with lipid solubility and as supporting the view that different anaesthetics act on different structures in the neuronal membranes to produce anaesthesia.
-
1 The purpose of this study was to investigate whether the separation between the hypotensive and sedative effects of a new series of centrally acting antihypertensive drugs was due to differences between the relative pre-junctional (alpha(2)) and post-junctional (alpha(1)) adrenoceptor agonist properties of the compounds.2 In anaesthetized rats the intravenous doses of clonidine, ICI 101187, ICI 106270, ICI 109683 and ICI 110802 required to lower blood pressure (BP) by 20 mm Hg were 1.2, 5.1, 5.5, 3.3 and 5.4 mug/kg respectively.3 In a test for sedation, ICI 101187 had at least 10 times less sedative effect than clonidine, ICI 106270 and ICI 109683 had at least 30 times less sedative effect than clonidine while ICI 110802 was not active. In a locomotor activity test the intravenous dose of clonidine required to reduce activity by 50% was 15.3 mug/kg, for ICI 101187 it was 194, for ICI 106270 it was 238 and for 110802 it was 313 mug/kg.4 In the pithed rat the ED(50)s of clonidine, ICI 101187, ICI 106270, ICI 109683 and ICI 110802 as alpha(2)-agonists were 19.4, 9.3, 63.2, 43.0 and 78.5 mug/kg respectively. The alpha(1)-adrenoceptor potencies were quite similar for the five drugs and varied between 3.2 mug/kg for ICI 110802 and 8.7 mu/kg for ICI 106720. ⋯ Clonidine and ICI 101187 were similar in potency with IC(50)s of 9.3 x 10(-9)m and 8.9 x 10(-9)m respectively. ICI 106270 and ICI 110802 were much weaker with IC(50)s of 4.9 x 10(-8)m and over 5.7 x 10(-8)m respectively.5 Since all the compounds had similar potencies as alpha(1)-agonists, this could not explain their different sedative effects. The weakest compounds as sedatives were also weakest as alpha(2)-agonists, although ICI 101187 which was as potent as clonidine as an alpha(2)-agonist was still 10 times weaker as a sedative.6 Hypotensive activity appears to be more closely related to alpha(1)- than to alpha(2)-potency.7 Clonidine was more potent as both a sedative and a hypotensive agent than would be predicted from its activity at either the alpha(1)- or the alpha(2)-adrenoceptor.
-
1. Phenytoin sodium, 10 micrograms/ml (3.6 x 10(-5) M), reduces the amplitude of endplate potentials in mouse sternomastoid neuromuscular junctions. 2. ⋯ The reduction caused by phenytoin in the amplitude of spontaneous miniature end plate potentials was due to a reduction in the time constant of decay of miniature endplate currents. 4. It is concluded that phenytoin depresses neuromuscular transmission by reducing both the amount of acetylcholine secreted in response to an action potential and by reducing the lifetime of postsynaptic channels activated by acetylcholine.
-
1 The effect of intravenous sodium salicylate on cerebral oxygen consumption and cerebral blood flow and its response to hypercapnia was measured by the 133Xenon intracarotid injection technique in ten baboons. 2 After an initial peak, the plasma salicylate level maintained a stable value for 2 h of 1 mmol/l with 50 mg/kg sodium salicylate and 2.5 mmol/l with 200 mg/kg sodium salicylate. 3 Sodium salicylate (50 mg/kg) produced no change in baseline cerebral blood flow (CBF) or cerebral oxygen consumption (CMRO2) but the CBF response to hypercapnia was reduced by 41% during the first hour. During the second hour after salicylate administration, CMRO2 increased by 26%, CBF at normocapnia increased by 31% and the CBF response to hypercapnia was 67% of the baseline value. 4 Sodium salicylate (200 mg/kg) increased CMRO2 by 65%. ⋯ The difficulties in interpreting changes in the CBF CO2 response in the presence of increases in CMRO2 are discussed. It is suggested that the respiratory stimulation seen in salicylate intoxication is the result of a central metabolic stimulation.