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Biomedical subjects

M S Clark

Publications and source records attributed to M S Clark.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and muscarinic activities of quinuclidin-3-yltriazole and -tetrazole derivatives.

The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]quinuclidinyl benzilate. Potency and efficacy were found in compounds in which the azole moiety was attached to the azabicyclic ring either through a carbon atom or a nitrogen atom. Electrostatic potential maps of both the C-linked and the novel N-linked series of compounds were calculated. A relationship between position and depth of the electrostatic minima relative to the azabicyclic ring and the potency and efficacy of the compounds was determined.

Animals↗
PubMed1991

Comparison of azabicyclic esters and oxadiazoles as ligands for the muscarinic receptor.

The link between the cognitive deficit associated with Alzheimer type dementia and the loss of cholinergic function in the disease provides a basis for examining muscarinic agonists as potential therapeutic agents. This paper describes the design and synthesis of novel azabicyclic methyl esters as ligands for the muscarinic receptor. Replacement of the methyl ester by a 3-methyl-1,2,4-oxadiazole ring produces potent metabolically more stable muscarinic agonists capable of penetrating the central nervous system. These compounds generally show improved affinity relative to the corresponding methyl esters. 3-Methyl-1,2,4-oxadiazole 7b has an affinity 4 times that of acetylcholine. Receptor affinity is discussed in relation to the size and geometry of the azabicyclic ring and the electronic properties of the heteroaromatic ring.

Aminoquinolines↗
PubMed1989

Providing help and desired relationship type as determinants of changes in moods and self-evaluations.

Observed in 2 initial studies was converging evidence that helping improves the helpers' moods and self-evaluations. In these studies Ss induced to help showed improved moods and self-evaluations relative to Ss not given an opportunity to help. A 3rd study examined the moderating effects of desired relationship type on reactions to having helped. In this study Ss were led to desire either a communal or an exchange relationship with another. They then helped the other or were not allowed to help. Among Ss led to desire a communal relationship, but not among those led to desire an exchange relationship, helping was associated with greater improvements in moods than not helping. Helping tended to improve self-evaluations regardless of desired relationship type. However, this effect reached statistical significance only among subjects led to desire a communal relationship.

Adolescent↗
PubMed1988

The selective dopamine antagonist properties of BRL 34778: a novel substituted benzamide.

BRL 34778, exo-4-amino-5-chloro-2-methoxy-N-[9-(4-fluorophenylmethyl)-9-azabi cyclo(3.3.1) non-3-yl]-benzamide, is a very potent and specific dopamine D2-receptor antagonist. It exhibits a Ki value of 2.14 nM for dopamine D2-receptors but much lower affinity for D1-(Ki 5700 nM) and for many other receptor types. Its action is potent and of long duration in models for antipsychotic activity (4 h ED50s PO are 0.017 mg/kg for antagonism of apomorphine-induced climbing in mice and 0.028 mg/kg for antagonism of amphetamine-induced locomotion in rats). In contrast to its high potency in models for antipsychotic activity, BRL 34778 is much weaker in models for extrapyramidal effects and sedation (4 h ED50s PO are 2.4 mg/kg for inducing catalepsy in rats and 1.14 mg/kg for inhibition of rearing behaviour in rats). These data indicate potent activity of BRL 34778 in models for antipsychotic activity but low activity in models for extrapyramidal effects and sedation.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Moods and compliance.

This study examined the impact of subjects' moods on their compliance with simple messages. It was predicted and found that recipients of messages: (1) complied more when in a happy mood than when in a neutral state, and (2) complied less when in an angry mood than when in a neutral state. These effects were observed both when high and low pressure messages were used. Possible boundary conditions for the observed effects are discussed.

Adult↗
PubMed1988

Structural complexity of Y chromosome heterochromatin.

Following a standard C-banding procedure early metaphase chromosomes demonstrate a discontinuous distribution of heterochromatin in the long arm of the human Y chromosome. The discrete blocks of heterochromatin can be shown to be separated into nonrepeating sequences by in situ hybridization using probe pHY 2.1. The number of heterochromatin blocks vary from person to person.

Chromosome Banding↗
PubMed1987

An evaluation of the clinical analgesia/anesthesia efficacy on acute pain using the high frequency neural modulator in various dental settings.

The purpose of this study was to evaluate the effectiveness of high frequency neural modulation as a substitute for traditional local anesthesia in various dental procedures. This double-blinded study was done to evaluate patient comfort and degree of satisfaction as well as manageability of pain control by the operator during the dental procedures. Procedures included restorations, tooth extractions, root planing, pulp extirpation, and temporomandibular joint therapy. In the experimental group, favorable responses ranged from 0.0% to 92.8%, depending on the procedures. An overall favorable rating of 71.8% was given by the experimental group, and an overall favorable response of 8.5% was given by the placebo group.

Acute Disease↗
PubMed1987

Midazolam, diazepam, and placebo as intravenous sedatives for dental surgery.

This study was a comparison of the sedative and amnestic properties of midazolam and diazepam when administered for relief of patient discomfort during dental surgery. It was a double-blind placebo-controlled group study, which entailed the analysis of 60 patients randomly assigned to the three groups: midazolam, diazepam, and placebo. There were 20 patients in each group. Midazolam patients showed superior performance in the parameters of sedation and amnesia when compared to patients who were administered diazepam. Both groups showed better results than the placebo group, which had the best results with the Digit Symbol Substitution Test and the Trieger Test.

Adolescent↗
PubMed1987

Recipient's mood, relationship type, and helping.

We conducted two studies to examine how a potential helper is affected by having a communal orientation toward a relationship with a potential recipient and by the potential recipient's sadness. We hypothesized that (a) having a communal orientation would increase helping and that (b) people high in communal orientation, but not others, would respond to a potential recipient's sadness by increasing helping. These hypotheses were tested in two studies. In Study 1, individual differences in communal orientation toward relationships were measured by using a new communal orientation scale reported for the first time in this article. In Study 2, manipulations were used to lead subjects to desire either a communal or an exchange relationship with another person. In both studies, subjects were exposed to a sad person or to a person in a neutral mood whom they were given a chance to help. As hypothesized, in both studies communally oriented subjects helped the other significantly more than did others. Also as hypothesized, in both studies communally oriented subjects but not others, increased helping in response to the other person's sadness although this effect reached statistical significance only in the second study.

Adult↗
PubMed1986

BRL 20596, a novel anilide with central dopamine antagonist activity.

BRL 20596 (N-(4-amino-5-chloro-2-methoxyphenyl)-1-phenylmethyl-4-piperidine-carbox amide) is a novel anilide related to clebopride (a gastric prokinetic benzamide) in which the sole change is reversal of the amide bond. Previous studies have shown conformational and electronic differences between these molecules which result in the anilide losing its gastric prokinetic activity, whilst retaining its central nervous system activity. Pharmacological and biochemical properties of BRL 20596 are compared here in animals with chlorpromazine, clebopride, haloperidol and sulpiride. BRL 20596 potently inhibited a number of behaviours, such as conditioned avoidance, amphetamine-induced stereotypy and turning, and apomorphine-induced climbing. Homovanillic acid (HVA) levels in the striatum and nucleus accumbens were raised at similar dose levels to those which inhibited these behaviours, whilst sedative activity was only exhibited at much higher dose levels. Haemodynamic changes were only observed with high IV doses of BRL 20596. Much lower doses of sulpiride were needed to raise prolactin levels than to raise HVA levels. This was not the case with BRL 20596 and the other drugs, where the doses needed for the two effects were similar. The results suggest that BRL 20596 is a central dopamine antagonist, with low sedative and haemodynamic activity.

Animals↗
PubMed1986

Social skills and the stress-protective role of social support.

Cross-sectional analyses of data collected from a large sample of incoming college freshmen were used to determine whether the perceived availability of social support protects persons from stress-induced depressive affect; whether social competence, social anxiety, and self-disclosure are responsible for the stress-protective effect of perceived social support; and whether these social skill measures discriminate among persons for whom support will help, hinder, or be ineffective in the face of stress. Prospective analyses based on the original testing (beginning of school year) and 11- and 22-week follow-ups of a randomly selected subsample were used to determine how the same social skill factors influence the development and maintenance of support perceptions and of friendships. Evidence is provided for a stress-buffering role of the perceived availability of social support. The stress-buffering effect is unaffected by controls for the possible stress-protective influences of social anxiety, social competence, and self-disclosure. Although these social skill factors do not discriminate among persons for whom support will help, hinder, or be ineffective, they are prospectively predictive of the development of both social support and friendship formation. These prospective relations between social skills and the development of perceived availability of social support are only partly mediated by number of friends.

Adolescent↗
PubMed1986

Keeping track of needs in communal and exchange relationships.

Keeping track of needs in communal and exchange relationships was investigated in two experiments. In both, subjects could check to see if another person needed help. The first experiment tested the hypotheses that When there is no opportunity for the other to reciprocate in kind, keeping track of the other's needs will be greater if the person desires a communal relationship with the other than if the person desires an exchange relationship with the other. If the person desires an exchange relationship with the other, keeping track of the other's needs will be greater when an opportunity for the other to reciprocate in kind exists than when it does not. If a communal relationship is desired, the existence of an opportunity for the other to reciprocate in kind will not influence keeping track of the other's needs. The results of the first experiment supported all three hypotheses. The second experiment tested and found support for the hypothesis that even when nothing can be done to help the other, keeping track of the other's needs will be greater if a communal relationship is desired with the other than if an exchange relationship is desired.

Dependency, Psychological↗