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M Williams

Publications and source records attributed to M Williams.

At least 685 records · Page 38Linked to original sources
PubMed1981

Further evidence for selective antagonism of taurine by 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide.

The putative taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide (TAG), was examined for activity in blocking contraversive turning evoked by the injection of taurine into the substantia nigra of the rat. Microinjected intranigrally as pretreatment to taurine, TAG caused a 71% reduction in taurine elicited turning. On the other hand, TAG pretreatment did not diminish the number of turns evoked by the intranigral injection of the GABA agonist, muscimol. These results and the lack of effect of TAG in a number of central radioligand binding assays provide further indications that TAG may be a selective taurine antagonist.

Animals↗
PubMed1981

Pharmacological profiles of the putative dopamine autoreceptor agonists 3-PPP and TL-99.

The putative dopamine (DA) autoreceptor agonists, N-n-propyl-3-(3-hydroxyphenyl)-piperidine (3-PPP) and 6, 7-dihydroxy-2-dimethylaminotetralin (TL-99) were compared with apomorphine in a series of tests indicative of DA receptor activation. All three agents displaced [3H] apomorphine and [3H] spiroperidol from DA recognition sites in rat brain and caused contralateral turning in the 6-hydroxydopamine lesioned rat. Apomorphine and TL-99 were generally more potent than 3-PPP. All three agents were also active at the DA autoreceptor that controls the synthesis of dopamine as indicated in vivo using the gamma-butyrolactone (GBL) procedure and in vitro using a synaptosomal preparation. In addition, all agents produced emesis in beagles. clear differences in the drugs' actions were observed in other test procedures. In the rat, apomorphine was the only compound which caused stereotypy or rotation following a reversible KCI-induced lesion of the striatum. Conversely, TL-99 and 3-PPP lacked activity in these procedures. Presumably, activity in these two tests indicates postsynaptic DA receptor activation. Each of the putative autoreceptor agonists produced a monotonic dose-related decrease in the mouse locomotor activity as opposed to the biphasic effect exerted by apomorphine. This action on the mouse locomotor activity, coupled with the results for the GBL test, provides an index of autoreceptor activation. In contrast to 3-PPP, both apomorphine and TL-99 increased locomotor activity in animals pretreated with reserpine and alpha-methyl-p-tyrosine and caused rotation in unilaterally caudectomized mice. In these test procedures thought to reflect activity at the postsynaptic DA receptor, TL-99 differed in its action from 3-PPP in a manner which suggests 3-PPP may be a more selective DA autoreceptor agonist.

4-Butyrolactone↗
PubMed1981

A comparison of the fears of mildly retarded adults with children of their mental age and chronological age matched controls.

Twenty mildly retarded adults were matched for chronological age and sex with twenty non-retarded children using the Peabody Picture Vocabulary Test. All 60 subjects were given an 89-item Fear Survey Schedule with a three-point rating scale. Mildly retarded adults were more fearful in general and showed a more intense level of fear than their chronological age matched controls. However, they reported less overall fear than their mental age matched controls. Differences in type of feared objects or situations were reported between groups. The importance of understanding the degree and types of fear in promoting de-institutionalization in the retarded is stressed.

Adult↗
PubMed1981

Interaction of putative anxiolytic agents with central adenosine receptors.

The benzodiazepine anxiolytics flurazepam and diazepam and CL 218872, zopiclone and two beta-carboline ethyl carboxyl esters, compounds which are potent displacers of specific [3H]diazepam binding from rat brain membranes, have little or no activity in displacing [3H]2-chloroadenosine ([3H]2-CADO) from central A1-adenosine receptors. Conversely, the purine agonists, 1-N6-phenylisopropyladenosine, N6-cyclohexyladenosine, 2-chloroadenosine, and the adenosine antagonist 8-phenyltheophylline have no significant effect on [3H]diazepam binding. Etazolate (SQ 20009) and Avermectin B1a which enhance [3H]diazepam binding in vitro were also without significant effect on [3H]2-CADO binding. The lack of correlation of the activities of the compounds examined in the two binding assays is discussed in relation to the hypothesis that purine-like compounds may be involved in the molecular mechanisms related to anxiolytic action at the receptor level.

Animals↗
PubMed1981

Heterogeneity of nuclear estrogen-binding sites in the rat uterus: a simple method for the quantitation of type I and type II sites by [3H]estradiol exchange.

Estrogen administration to mature-ovariectomized rats causes the activation or stimulation of secondary nuclear estrogen-binding sites (type II) in the uterus which can interfere with estrogen receptor (type I) measurement. Earlier reports from our laboratory have shown that quantitation of type I sites in the presence of the type II site is very difficult and can only be achieved by graphic analysis of saturation curves which employ a wide range (0.4-40 NM) of [3H]estradiol concentrations in nuclear exchange assay. The studies presented in this manuscript describe simple methods which can be used to separately quantitate both nuclear estrogen-binding sites using a single concentration of [3H]estradiol. Since the nuclear type II site does not bind [3H]estradiol in the presence of reducing agent, type I sites can be easily quantitated by incubating nuclei (37 C for 30 min) in Tris-EDTA buffer containing 0.1-1.00 mM dithiothreitol using a single saturating concentration of [3H]estradiol. Conversely, a single concentration of [3H]estradiol (40-80 nM) can be used to quantitate the nuclear type II site by incubating nuclei in Tris-EDTA buffer under conditions (4 C for 60 min) which do not measure occupied nuclear estrogen receptor. Therefore, by using the appropriate buffer system, type I and type II sites can be easily separated in mixed binding systems. In addition, we also demonstrate that Nafoxidine does not bind to the nuclear type II site. Therefore, it can be used as a competitive inhibitor of [3H]estradiol binding to type I sites and permit the measurement of type II sites without interference from type I sites. These techniques should be applicable to autoradiographic or fluorescence studies which cannot discriminate between steroid binding to these two classes of nuclear estrogen-binding sites.

Animals↗
PubMed1981

Anthelmintic activities of ivermectin against gastrointestinal nematodes of cattle.

The anthelmintic efficacy of ivermectin, a combined solution of the B1a and B1b fractions of avermectin, was assessed in a controlled trial. Twenty-four yearling calves experiencing naturally acquired, clinical gastrointestinal helminthiasis were evenly divided on the basis of weight into two 12-animal groups. The medicated group was given (subcutaneously) ivermectin at the dose rate of 200 microgram/kg of body weight. The control animals were given the vehicle alone, at an equivalent rate. All animals were killed 14 days later. At necropsy of the calves, gastrointestinal helminth arithmetic means were 178,626 and 575 for the control and the treated groups, respectively, an overall reduction of 99.7%. Nematodes which were present at substantial levels were Ostertagia ostertagi, O lyrata, Trichostrongylus axei, Cooperia punctate, C oncophora, C mcmasteri, and Oesophagostomum radiatum. Anthelmintic activity of ivermectin was excellent regardless of nematode species, sex, or stage of development.

Animals↗
PubMed1981

We did it at U-M.

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Michigan↗