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Biomedical subjects

A C Lane

Publications and source records attributed to A C Lane.

33 records · Page 2Linked to original sources
PubMed1986

The mode of antifungal action of tolnaftate.

The anti-dermatophyte agent tolnaftate was compared with the allylamine antifungal compounds naftifine and terbinafine. Tolnaftate was shown to inhibit sterol biosynthesis at the level of squalene epoxidation and squalene was shown to accumulate in dermatophytes grown in its presence. Biochemical studies in whole and broken cells supported this conclusion and showed that the compound was active against squalene epoxidation in broken C. albicans cells, but was much less potent against whole cells. These results suggested there was a barrier to penetration in these yeasts.

Allylamine↗
PubMed1984

Effects of idazoxan on catecholamine systems in rat brain.

Experiments have been performed to assess the potency of idazoxan (RX 781094) at alpha and beta-adrenoceptors and dopamine receptors and on catecholamine uptake processes in rat brain. The effects of idazoxan on the turnover rates of noradrenaline and dopamine have been determined. Radioligand binding studies with cerebral cortex membranes have demonstrated that idazoxan exhibits 46-fold selectivity for alpha 2-adrenoceptors labelled by (3H)-idazoxan (Mean Ki +/- S.E.M. = 3.1 +/- 0.4 nM) compared with alpha 1-adrenoceptors labelled by (3H)-prazosin (Mean Ki +/- S.E.M. = 142 +/- 27 nM). Under the same conditions, yohimbine showed 6-fold selectivity for alpha 2-adrenoceptors. Idazoxan had low affinity for beta-adrenoceptors labelled by (3H)-dihydroalprenolol (IC50 value greater than 10 microM), for dopamine receptors labelled by (3H)-domperidone (IC50 value greater than 20 microM), for the (3H)-noradrenaline uptake site in rat hypothalamus (IC50 = 31 microM) and for the (3H)-dopamine uptake site in rat striatum (IC50 value approximately 800 microM). In rats treated with alpha-methyl-p-tyrosine, idazoxan (10-80 mg/kg, po) produced a marked increase (63% at 10, 217% at 20 mg/kg, po) in the apparent rate of turnover of noradrenaline in rat cortex/striatum, without affecting the rate of turnover of dopamine. This was in contrast to yohimbine (5-20 mg/kg, po) which increased the turnover rates of both catecholamines. In the absence of alpha-methyl-p-tyrosine, idazoxan (5-40 mg/kg, po) produced a dose related increase in the MHPG concentration and a small (20-30%) reduction in the steady state concentration of NA; the duration of the reduction was dose-related. DA steady state concentrations were unaffected. Idazoxan is a new selective alpha 2-adrenoceptor antagonist which should prove a valuable investigative tool in neurochemical studies and which may be a useful clinical agent in the management of the affective disorders.

Adrenergic alpha-Antagonists↗
PubMed1984

Comparison of the alpha-adrenoceptor antagonist profiles of idazoxan (RX 781094), yohimbine, rauwolscine and corynanthine.

In the present studies the potency and selectivity of idazoxan (RX 781094) were compared with yohimbine and its diastereoisomers rauwolscine and corynanthine in both functional studies and radioligand binding experiments. Prejunctional alpha 2- and postjunctional alpha 1-adrenoceptor antagonist potencies were assessed by determining pA2 values against clonidine on the stimulated rat was deferens and noradrenaline on the anococcygeus muscle, respectively. The rank order of prejunctional alpha 2-adrenoceptor antagonist potency was idazoxan greater than yohimbine greater than rauwolscine much greater than corynanthine. At postjunctional alpha 1-adrenoceptors the rank order of antagonist potency was rauwolscine greater than corynanthine greater than yohimbine greater than idazoxan. The selectivity values (alpha 2/alpha 1) for idazoxan, yohimbine, rauwolscine and corynanthine were 245, 45, 3 and 0.03 respectively. The selectivity and potency profiles established for these antagonists in functional studies were confirmed in radioligand binding studies utilising 3H-idazoxan (alpha 2) and 3H-prazosin (alpha 1) in rat cerebral cortex. In pithed rats intravenously administered idazoxan, yohimbine and rauwolscine fully reversed the inhibitory effects of clonidine on electrically-induced contractions of the vas deferens; idazoxan was approximately ten times more potent than both yohimbine and rauwolscine. Corynanthine was inactive. Idazoxan and yohimbine also fully antagonised the inhibitory effects of guanabenz on electrically-induced contractions of the anococcygeus muscle; idazoxan again was more than ten times more potent than yohimbine in this model. The inhibitory effects of guanabenz were less readily antagonised by rauwolscine indicating that the selectivity of this compound is less than that of yohimbine in this tissue. Corynanthine was again inactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1984

2-Alkyl analogue of idazoxan (RX 781094) with enhanced antagonist potency and selectivity at central alpha 2-adrenoceptors in the rat.

Four 2-alkyl (methyl, ethyl, n-propyl and isopropenyl) analogues of idazoxan (RX 781094) have been synthesized and assessed in terms of their central alpha 2/alpha 1-adrenoceptor selectivity and alpha 2-adrenoceptor antagonist potency using both in vitro and in vivo tests in the rat. In cortical binding assays using [3H]-idazoxan and [3H]-prazosin, idazoxan had a 5 times greater alpha 2/alpha 1-selectivity than yohimbine. The 2-alkyl substituted analogues all showed improved selectivity, being between 17 and 29 times more selective than yohimbine for [3H]-idazoxan binding sites. In terms of central antagonist potency in vivo, the most favourable substitutions were 2-ethyl (RX 811033) and 2-n-propyl (RX 811054). Compared with yohimbine, these analogues were, respectively, 36 and 18 times more potent intravenously and 5 and 7.5 times more potent orally in their antagonism of guanoxabenz-induced mydriasis in the pentobarbitone-anaesthetized rat. All the analogues had a duration of action similar to that of idazoxan, which was significantly shorter than that of yohimbine. The results indicate that introduction of alkyl groups in the 2-position of idazoxan greatly increases the alpha 2/alpha 1-adrenoceptor selectivity as measured in binding studies. Improved alpha 2-adrenoceptor affinity and antagonist potency were particularly associated with the 2-ethyl and 2-n-propyl analogues.

Adrenergic alpha-Antagonists↗
PubMed1984

Subjective and objective features of sore throat.

This study examines the relationship between the symptom of sore throat and the signs of pharyngitis. Patients seeking medical attention for sore throat were examined by their physician, who documented findings on a Tonsillopharyngitis Score (TPS) and obtained a throat culture. Each patient was then instructed by the physician's assistant to characterize the severity of throat pain on a Sore Throat Pain Intensity Scale (STPIS) and Sore Throat Questionnaire. A high positive correlation was found for the STPIS and TPS but not for these findings and the cause of pharyngitis. A similar association was found between the relative severity of throat pain and the words patients use to describe it. This new method objectively confirms the subjective rating of sore throat pain.

Adolescent↗
PubMed1983

Evidence for pharmacological similarity between alpha 2-adrenoceptors in the vas deferens and central nervous system of the rat.

Seven alpha 2-adrenoceptor antagonists with diverse chemical structures have been examined for their effects at alpha 2-adrenoceptors in the vas deferens and central nervous system of the rat. Antagonist potency assessed against the presynaptic alpha 2-adrenoceptor agonist action of clonidine in the isolated vas deferens (RX 781094 greater than Wy 26703 greater than yohimbine greater than rauwolscine greater than piperoxan greater than mianserin greater than RS 21361) was highly correlated with the ability of these drugs to displace saturable [3H]-RX 781094 binding from cerebral cortex membranes. Similarly, antagonist potency in the vas deferens was highly correlated with antagonist activity in reversing the centrally-mediated mydriasis induced by the selective alpha 2-adrenoceptor agonist, guanoxabenz, in pentobarbitone-anaesthetized rats. The results indicate that the presynaptic alpha 2-adrenoceptors in the vas deferens are pharmacologically similar to characterized these alpha 2-adrenoceptors in the central nervous system of the rat.

Adrenergic alpha-Antagonists↗
PubMed1982

Common anionic receptor site hypothesis: its relevance to the antagonist action of naloxone.

Appropriate modification of 14 beta-methoxy- and 14 beta-ethoxycodeinone (prepared by alkylation of 14 beta-hydroxycodeinone) has generated four alkoxy analogues (3a-d) of naloxone and naltrexone. These agents were pure narcotic antagonists in contradiction to the predictions of the common anionic receptor site hypothesis, postulated to be of importance in the enhanced antagonism of naloxone. The molecular change from allyl to cyclopropylmethyl on the N atom increased selectivity of these antagonists for the mu receptor to the same extent as found for naloxone. Increase in the length of the C14 O-substituent had no effect on receptor selectivity, and either formation in most cases did not significantly alter oral/parenteral ratios of durations of action.

Animals↗
PubMed1975

[Transport and mode of action of sennosides].

Prior to attempting to develop a new laxative, pharmacodynamic studies were conducted on the individual active constituents of senna. Sennoside A, sennoside B and rhein were injected intravenously and were introduced into the isolated stomach, small bowel and large bowel of the anaesthetised pig. Blood, urine and bile, collected over 6 hours, were assayed by a novel fluorometric technique. Recoveries and measured oil water partition coefficients indicate that the sennosides are virtually non-absorbed in the stomach and small bowel. Following administrations outside the large bowel, anthracene derivative concentrations in the lumen and wall of the colon were below the limits of detection. Thus, a transport theory involving absorption and resecretion of sennosides into the large bowel is discounted. The results support a mode of action involving direct transport through the alimentary canal to the large bowel where micro-organism break the sugar-anthracene bonds. Derivatives of the liberated lipophilic aglycones are absorbed into the wall of the colon and stimulate the nerve plexuses thereby leading to defaecation. The "colon-specific" mode of action of the natural anthrone glycosides appears to be an ideal method of stimulating bowel action.

Animals↗