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W E Sneader

Publications and source records attributed to W E Sneader.

12 recordsLinked to original sources
PubMed1994

Pharmacological studies on new potential local anesthetics.

The results of the pharmacological screening of a series of new basic aminoalkyl aryl ethers are reported. The anesthetic effects of these compounds were evaluated by the guinea pig intradermal wheal test. Lidocaine was used as the standard and normal saline as the control. These were, generally, better than or as good as the standard, in terms of potency, onset of action, duration of effect, time of full recovery from complete anesthesia and lack of both apparent local and systemic side effects. The duration of action of their local anesthesia has shown a strong dependence on the substitution pattern of the compounds. Moreover, it seems that these compounds act selectively and reversibly by blocking nervous conduction at a localized area, as small as a skin wheal, without any obvious deleterious untoward reactions, i.e. they are structurally specific and act at the neuronal channels (receptor sites). Thus, due to their outstanding local anesthetic profiles, it is worthy to conduct additional studies on these agents, as potential candidates for the treatment of intolerable chronic pain, which does not respond to mild analgesic drugs, and other available medicines.

Anesthetics, Local↗
PubMed1991

Pharmacological and microbiological evaluations of potential new long-acting local anaesthetics.

The results of the preliminary pharmacological and microbiological evaluations of certain new derivatives of dialkylaminoethyl-phenyl-ether hydrochloride, as potential long-acting local anaesthetics, are reported. The guinea pig intradermal wheal test was used for determining the activity and duration of local anaesthesia (WT). These were assayed at concentrations of 0.5% w/v. Lidocaine hydrochloride, 1.0% w/v, was employed as the standard and normal saline, 0.9% w/v, as the control. The compounds showed outstanding activity profiles and duration of action with no apparent signs of both local and systemic side effects. In addition, the results of inhibition of the ciliated protozoan Tetrahymena pyriformis mobility by the aforementioned compounds are presented. A general relationship between the minimum inhibitory concentration (MIC) of these compounds to inhibit mobility of the whole T. pyriformis cells and the duration of anaesthesia was observed. Moreover, derivatives with tertiary or secondary butyl substituents in the benzene ring, irrespective of position or number, were superior to others and showed prolonged duration of anaesthesia and lower MIC. The dependence of both WT and MIC on partition coefficient (log P) of these compounds indicates that in both biological systems the anaesthetics interact strongly with hydrophobic structures of the T. pyriformis cells membrane resulting in fluidisation and loss of ciliary function.

Anesthetics, Local↗
PubMed1991

Pharmacological evaluation of certain novel prolonged-acting local anaesthetics. In vivo rat sciatic nerve block.

Some new 2-phenoxyethyldialkylamines in previous studies had proved to be superior to other standard drugs in respect of local anaesthetic activity. To confirm their intensity and duration of action, the two outstanding compounds were selected for further pharmacological studies on the rat sciatic nerve preparation in vivo. Their activity and duration of action were determined by a double-blind controlled trial (at the later stage) and in two stages. The test compounds showed comparable rates of onset of motor analgesia (5-10 min). They also displayed quick recovery from complete analgesia, typically being around 10 min after the first sign of a recovery of motor function was observed. In addition, no systemic or local untoward effects were noticed. Bupivacaine produced drowsiness in the rats.

Anesthetics, Local↗
PubMed1991

Studies on the drug binding of certain novel potential local anaesthetics.

One of the many factors affecting the response of an individual to a drug is the modification of its action by tissue and plasma proteins. Plasma proteins can be divided into three categories, viz., fibrinogen, globulins and albumin. Fibrinogen exhibits little reactivity with respect to drugs, being concerned solely with blood clotting, whereas globulins may have affinity for various endogenous compounds. Albumin, which constitutes around 4% of human serum, has the capability to bind reversibly or irreversibly to a wide range of substances. Generally, it has been found that albumins are particularly responsible for binding of local anaesthetics in plasma, but another binding factor may be lipoproteins present in blood cell membranes. Moreover, the transport of local anaesthetics to the site of action in the nerve membrane is influenced by their affinity for proteins present in extracellular fluids either at the site of injection, or surrounding the nerve fibres. Accordingly, systematic investigations on the protein binding characteristics of certain novel potential local anaesthetics was initiated with a view to ascertaining whether the duration of action of local anaesthetics could be correlated with their affinity for protein. The technique of equilibrium dialysis was used for measurements of drug-protein binding. This consists basically of two compartments separated by a semi-permeable cellulose membrane through which only free, unbound drug molecules can diffuse. The results indicate that there is no significant relationship between the extent of drug-protein binding and duration of local anaesthesia produced by these test compounds in the intradermal wheal test on the guinea-pig.

Anesthetics, Local↗
PubMed1979

Enhancement of methotrexate absorption by subdivision of dose.

A comparison was made in fasting patients between a single 100 mg oral dose of methotrexate formulated as its sodium salt in a palatable syrup and the same total quantity of drug administered in four divided doses of 25 mg taken at 2-h intervals. Allocation to the order of these treatment schedules was on a random basis. The area under the serum methotrexate concentration-time curve until 50 h was found to be considerably greater after the divided dose regimen, the mean ratio AUC 25 mg x 4/AUC 100 mg being 1.86 (+/- 0.90). There was no significant difference in peak serum methotrexate concentrations or methotrexate half-life estimates between the two regimens, however. The results of this study are consistent with saturation of an intestinal transport process when methotrexate is administered orally in a single large dose.

Half-Life↗