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M D Wood

Publications and source records attributed to M D Wood.

At least 37 records · Page 2Linked to original sources
PubMed1999

Personality factors moderate subjective and psychophysiological responses to d-amphetamine in humans.

The aim of the present study was to examine the relationship between measures of novelty and sensation seeking and both psychophysiological and subjective measures of stimulation after a pharmacological challenge with an indirect dopamine agonist, d-amphetamine. Prepulse inhibition (PPI) of the startle reflex and subjective responses were assessed after the challenge. The results indicated that the Novelty Seeking scale of the Tridimensional Personality Questionnaire (TPQ; M. Zuckerman, 1994). TPQ was a significant predictor of lower PPI and greater subjective stimulation. The Disinhibition scale of the Sensation Seeking Scale (SSS; M. Zuckerman, S. B. G. Eysenck, & M. J. Eysenck, 1978) moderated the effects of amphetamine on stimulation and elation, whereas the Boredom Susceptibility and Experience Seeking subscales of the SSS moderated subjective stimulation. These findings indicate that higher scores on novelty and sensation seeking correspond to heightened sensitivity to the effects of a stimulant medication.

Adult↗
PubMed1999

Functional comparison of muscarinic partial agonists at muscarinic receptor subtypes hM1, hM2, hM3, hM4 and hM5 using microphysiometry.

1. This study describes the pharmacological comparison of the muscarinic partial agonists sabcomeline, xanomeline and milameline at human cloned muscarinic receptor subtypes (hM1-5). 2. Radioligand binding studies at the hM1-5 muscarinic receptor subtypes were compared with functional studies using microphysiometry using carbachol as the standard full agonist. 3. In binding assays none of the compounds studied displayed preferential affinity for the M1,3,4 or M5 subtypes although carbachol was less potent at hM1 than hM3,4,5. 4. In functional studies, all of the compounds studied displayed similar levels of efficacy across the muscarinic receptors with the exception of M3, where there was a large apparent receptor reserve and the compounds behaved essentially as full agonists. 5. Sabcomeline was the most potent agonist in functional studies but also showed the lowest efficacy. In terms of potency, xanomeline showed some selectivity for M1 over M2 receptors and milameline showed some selectivity for M2 over M1 receptors. 6. These results show the value of microphysiometry in being able to compare receptor pharmacology across subtypes irrespective of the signal transduction pathway. 7. None of the partial agonists showed functional selectivity for M1 receptors, or indeed any muscarinic receptor, in the present study.

Animals↗
PubMed1999

Psychosocial correlates of voluntary HIV antibody testing in college students.

Although past research has examined correlates of HIV testing, much of it has focused on demographic differences between tested and nontested individuals. The present study examined psychosocial differences between individuals seeking a voluntary HIV test at a college student health center and individuals who have never had an HIV test. Variables included in the model were four components of the health belief model (perceived susceptibility, perceived severity, perceived benefits, perceived barriers), as well as perceived norms, consideration of future consequences, and risky sexual behavior. Results suggest that individuals seeking an HIV test perceived more benefits of having a test, tended to perceive fewer barriers to having a test, were higher in consideration of Future Consequences, and engaged in riskier sexual behavior than individuals never having had an HIV test. Implications for both HIV testing interventions and the health belief model are discussed.

AIDS Serodiagnosis↗
PubMed1998

Novel and selective 5-HT2C/2B receptor antagonists as potential anxiolytic agents: synthesis, quantitative structure-activity relationships, and molecular modeling of substituted 1-(3-pyridylcarbamoyl)indolines.

The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB-206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT2C/2B receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT2C receptor but disallowed at the 5-HT2A receptor, we have identified a number of compounds which are the most potent and selective 5-HT2C/2B receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT2C receptor model and our proposed binding mode for this class of ligands within that model.

Animals↗
PubMed1998

Gamma-aminobutyric acidA receptor function is desensitised in rat cultured cerebellar granule cells following chronic flunitrazepam treatment.

This study examined gamma-aminobutyric acidA (GABA(A)) receptor function in cultured rat cerebellar granule cells by using microphysiometry following chronic flunitrazepam exposure, and correlated the findings with the alpha1 and beta2/3 subunit protein expression and [3H]muscimol binding after the same treatment paradigm. Flunitrazepam treatment reduced (p < 0.05) the maximal GABA-stimulated increase in extracellular acidification rate (Emax) (16.5 +/- 1.2% and 11.3 +/- 1.0%, 2-day control and treated cells, respectively; 17.4 +/- 1.0% and 9.9 +/- 0.7%, 7-day control and treated cells, respectively; best-fit Emax +/- SEM, n = 7), without affecting the GABA concentration required to elicit 50% of maximal response (EC50) (1.2 +/- 1.7 and 2.3 +/- 1.8 microM, 2-day control and treated cells, respectively; 1.7 +/- 1.5 and 1.5 +/- 1.5 microM, 7-day control and treated cells, respectively; best-fit EC50 +/- SEM, n = 7). Flunitrazepam exposure also abolished the flunitrazepam potentiation of the GABA response, caused a transient reduction of the GABA(A) receptor alpha1 and beta2/3 subunit proteins over the initial 2 days, but did not alter [3H]muscimol binding compared with vehicle-treated cells. The results suggest that changes in GABA(A) receptor subunit protein expression, rather than loss of [3H]muscimol binding sites, underlie the chronic flunitrazepam-mediated desensitisation of GABA(A) receptor function.

Acids↗
PubMed1998

Bilateral vocal cord paralysis following anterior cervical discectomy and fusion. Case report.

The authors report a rare case of bilateral vocal cord paralysis following anterior cervical discectomy and fusion (ACD/F) in a patient who had a preexisting, clinically silent, and unrecognized unilateral vocal cord paralysis from a remote cardiac surgical procedure. The patient, a 41-year-old woman who developed acute respiratory stridor and respiratory insufficiency at the time of extubation after undergoing a C6-7 ACD/F, required emergency reintubation and ventilation. Otolaryngological evaluation revealed bilateral vocal cord paralysis with one vocal cord showing evidence of acute paralysis and the other showing evidence of chronic paralysis. She eventually required a permanent tracheotomy. The patient had undergone previous cardiac surgical procedures to correct Fallot's tetralogy as a neonate and as a child. At those times, there were no recognized symptoms of transient or permanent vocal cord dysfunction. This case emphasizes the importance of identifying patients with preexisting unilateral vocal cord paralysis before performing neurosurgical procedures such as ACD/F, which can place the only functioning vocal cord at risk for paralysis. Guidelines for identifying patients with preexisting unilateral vocal cord paralysis and for modifying the surgical procedure for ACD/F to prevent the catastrophic complication of bilateral vocal cord paralysis are discussed.

Adult↗
PubMed1997

Measurement of GABAA receptor function in rat cultured cerebellar granule cells by the Cytosensor microphysiometer.

1. gamma-Aminobutyric acid (GABA), acting via the GABAA receptor, increased the extracellular acidification rate of rat primary cultured cerebellar granule cells, measured by the Cytosensor microphysiometer. 2. The optimal conditions for the measurement of GABAA receptor function in cerebellar granule cells by microphysiometry were: cells seeded at 9-12 x 10(5) cells/transwell cup and maintained in vitro for 8 days, GABA stimulation performed at 25 degrees C, with a stimulation time of 33 s. 3. GABA stimulated a concentration-dependent increase in the extracellular acidification rate with an EC50 of 2.0 +/- 0.2 microM (mean +/- s.e.mean, n = 7 experiments) and maximal increase (Emax) over basal response of 15.4 +/- 1.2%. 4. The sub-maximal GABA-stimulated increase in acidification rate could be potentiated by the 1,4-benzodiazepine, flunitrazepam (100 nM). The 10 nM GABA response showed the maximal benzodiazepine facilitation (GABA alone, 1.4 microV s-1, GABA + flunitrazepam, 3.8 microV s-1, mean increment over basal, n = 7). 5. The GABA-stimulated increase in acidification rate was inhibited by the GABAA antagonist, bicuculline (100 microM) (90% inhibition at 1 mM GABA). 6. The results of this study show that activation of GABAA receptors in rat cerebellar granule cells caused an increase in the extracellular acidification rate; an effect which was potentiated by benzodiazepines and inhibited by a GABAA receptor antagonist. This paper defines the conditions and confirms the feasibility of using microphysiometry to investigate GABAA receptor function in primary cultured CNS neurones. The microphysiometer provides a rapid and sensitive technique to investigate the regulation of the GABAA receptor in populations of neurones.

Animals↗
PubMed1996

Synthesis, biological activity, and molecular modeling of selective 5-HT(2C/2B) receptor antagonists.

The synthesis and biological activity are reported for a series of analogues of the previously published indole urea 2 (SB-206553), designed to probe the 5-HT(2C) receptor binding site. Small molecule modeling studies have been used to define a region in space which is allowed at the 5-HT(2C) receptor but disallowed at the 5-HT(2A) receptor. In a complementary approach, docking of 2 into our model of the 5-HT(2C) receptor has allowed us to propose a novel primary binding interaction for this series of diaryl ureas, involving a potential double hydrogen-bonding interaction between the urea carbonyl oxygen of the ligand and two serine residues in the receptor. The difference of two valine residues in the 5-HT(2C) receptor for leucine residues in the 5-HT(2A) receptor is believed to account for the observed 5-HT(2C)/5-HT(2A) selectivity with 2.

Animals↗
PubMed1996

m-Chlorophenylpiperazine (mCPP) is an antagonist at the cloned human 5-HT2B receptor.

The behavioural effects of m-chlorophenylpiperazine (mCPP) in rats and its clinical effects in man are thought to be related to its action at 5-HT2B/2C receptors. However, although mCPP is a partial agonist at these subtypes in rat, its efficacy at human 5-HT2B/2C receptors is unknown. We therefore investigated the activity of mCPP at cloned human 5-HT2B and 5-HT2C receptors. mCPP was a partial agonist at the human 5-HT2C receptor but antagonized the human 5-HT2B receptor. Therefore, while supporting the proposal that at least some of the clinical effects of mCPP are likely to be mediated via stimulation of the 5-HT2C receptor, this study also suggests that any 5-HT2B receptor-mediated effects are more likely to result from receptor blockade than from receptor activation.

Animals↗
PubMed1996

Hematosalpinx with pelvic pain after endometrial ablation confirms the postablation-tubal sterilization syndrome.

Complications after endometrial ablation are uncommon, and published series show that the majority of women who are treated by this technique remain symptom free in the postoperative period. A 39-year-old woman with previous tubal ligation underwent laparoscopic-assisted vaginal hysterectomy for debilitating pelvic pain 1 year after endometrial ablation. Pathologic assessment of the surgical specimen showed bilateral hematosalpinges from continued cyclic occult bleeding. The symptoms and findings in this case confirm the postablation-tubal sterilization syndrome.

Adult↗
PubMed1996

In vitro and in vivo profile of SB 206553, a potent 5-HT2C/5-HT2B receptor antagonist with anxiolytic-like properties.

1. SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2 ,3-f]indole) displays a high affinity (pK1 7.9) for the cloned human 5-HT2C receptor expressed in HEK 293 cells and the 5-HT2B receptor (pA2 8.9) as measured in the rat stomach fundus preparation. SB 206553 has low affinity for cloned human 5-HT2A receptors expressed in HEK 293 cells (pK1 5.8) and (pK1 < 6) for a wide variety of other neurotransmitter receptors. 2. SB 206553 appears to be a surmountable antagonist of 5-HT-stimulated phosphoinositide hydrolysis in HEK 293 cells expressing the human 5-HT2C receptor (pKB 9.0). 3. The compound potently (ID50 5.5 mg kg-1, p.o., 0.27 mg kg-1, i.v.) inhibited the hypolocomotor response to m-chlorophenylpiperazine (mCPP), a putative model of 5-HT2C/5-HT2B receptor function in vivo. 4. At similar doses (2-20 mg kg-1, p.o.) SB 206553 increased total interaction scores in a rat social interaction test and increased punished responding in a rat Geller-Seifter conflict test. These effects are consistent with the possession of anxiolytic properties. 5. SB 206553 also increased suppressed responding in a marmoset conflict model of anxiety at somewhat higher doses (15 and 20 mg kg-1, p.o.) but also reduced unsuppressed responding. 6. These results suggest that SB 206553 is a potent mixed 5-HT2C/5-HT2B receptor antagonist with selectivity over the 5-HT2A and all other sites studied and possesses anxiolytic-like properties.

Animals↗
PubMed1996

Alcohol outcome expectancies and alcohol use and problems.

OBJECTIVE: Numerous studies have demonstrated that alcohol outcome expectancies are strong correlates of various aspects of alcohol use. However, it has been suggested that forced-choice alcohol expectancy items may not measure the most salient anticipated effects of alcohol for an individual, and thus may create superficial responses. Additionally, research on attitude-behavior consistency has demonstrated that the nature of how an attitude is elicited can lead to attitudes that are more or less cognitive. The present study examined the applicability of this aspect of attitude theory to the study of alcohol outcome expectancies and the utility of self-generated outcome expectancies and subjective evaluations in predicting alcohol use and problems. METHOD: In an extension of methodology previously used in attitude research, alcohol-using college students (N = 165, 87 female) generated alcohol expectancies in response to two sentence stems designed to elicit "affectively" and "cognitively" based alcohol expectancies and made subjective evaluations (SE) ratings of each item generated on dimensions of positivity, likelihood and immediacy. RESULTS: While no support was found for the generalizability of a particular aspect of attitude theory, several interesting findings emerged. SE ratings were significantly related to measures of alcohol use and problems and, for alcohol use measures, predicted comparably to a standardized measure of expectancies. For alcohol dependence symptoms, the number of expectancies generated predicted significant unique variance over that accounted for by subjective evaluations. CONCLUSIONS: These results indicate that the sheer number of alcohol expectancies accessible to an individual may be an important correlate of alcohol dependence, independent of subjective evaluations.

Adult↗
PubMed1995

5-Methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole: a novel 5-HT2C/5-HT2B receptor antagonist with improved affinity, selectivity, and oral activity.

The preparation of a series of conformationally restricted analogues of indolylurea 1, namely tetrahydropyrroloindoles and tetrahydropyrroloquinolines, is described. The binding affinities of these compounds at 5-HT2A, 5-HT2B, and 5-HT2C receptors were determined. Of these compounds, the 1,2,3,5-tetrahydropyrrolo[2,3-f]indole derivative, compound 11, was found to have high affinity for the 5-HT2C (pKI 8.0) and 5-HT2B receptors (pA2 8.5), with excellent selectivity over the 5-HT2A and various other receptors (pKI < 6). 11 is also considerably more active than 1 in both an in vitro functional model, 5-HT-stimulated phosphoinositol hydrolysis (pKB 8.8), and an in vivo functional model, mCPP-induced hypolocomotion (ID50 5.5 mg/kg po). 11 should therefore be of significant utility as a pharmacological tool to delineate the functional significance of blockade of 5-HT2B and 5-HT2C receptors.

Administration, Oral↗
PubMed1994

Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C/2B receptor function.

Chronic treatment with selective 5-HT reuptake inhibitors (SSRI) are therapeutic in obsessive compulsive disorder, depression, anxiety, bulimia nervosa and migraine. In the present study the possibility that SSRI's act by desensitizing 5-HT2C/5-HT2B receptors was assessed using a putative in vivo model of 5-HT2C/5-HT2B receptor function, mCPP-induced hypolocomotion. mCPP (2, 4 and 6 mg/kg i.p. 20 min pretest) reduced locomotion and rears in rats treated acutely or chronically with saline. Acute oral administration of the SSRI's fluoxetine (10 mg/kg), paroxetine (10 mg/kg), or clomipramine (70 mg/kg) or the noradrenaline reuptake inhibitor, desipramine (10 mg/kg), all 1 hr pretest, did not prevent mCPP-induced hypolocomotion. In contrast, chronic treatment with the SSRI's paroxetine and fluoxetine (both 10 mg/kg p.o. daily x 21 days), significantly attenuated the effect of mCPP (4 and 6 mg/kg i.p.) on locomotion and rears 24 hr after the last pretreatment dose. Chronic clomipramine (70 mg/kg p.o. daily x 21 days) also significantly attenuated the effect of mCPP (4 mg/kg i.p.) on rears and tended to reduce the hypolocomotor response. However, chronic treatment with desipramine, (10 mg/kg p.o. daily x 21) had no effect on any of the parameters measured. As chronic fluoxetine and paroxetine did not reduce brain mCPP levels (determined by HPLC 30 min after 4 mg/kg i.p.) the results suggest that chronic SSRI's, but not desipramine, reduce 5-HT2C/5-HT2B receptor responsivity. If this occurs in man, it may mediate or contribute to their reported therapeutic efficacy in depression, anxiety, bulimia, migraine and alcoholism. It may also be of particular relevance to their unique efficacy in OCD.

Animals↗
PubMed1994

In vivo properties of SB 200646A, a 5-HT2C/2B receptor antagonist.

1. SB 200646A, N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride, the first reported selective 5-HT2C/2B over 5-HT2A receptor antagonist, (pK1 rat 5-HT2C receptor 6.9, pA2 rat 5-HT2B receptor 7.5, pK1 rat 5-HT2A receptor 5.2) dose-dependently blocked a putative rat model of 5-HT2C receptor activation; 1-(3-chlorophenyl)piperazine (mCPP, 5 mg kg-1, i.p. 20 min pretest)-induced hypolocomotion (estimated ID50 19.2 mg kg-1, p.o.). 2. SB 200646A also blocked another putative in vivo model of 5-HT2C receptor function; mCPP (5 mg kg-1, i.p. 20 min pretest)-induced hypophagia in 23 h food-deprived rats (estimated ID50 18.3 mg kg-1, p.o.). 3. SB 200646A did not antagonize 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced head shakes in rats at doses up to 200 mg kg-1, p.o., an effect thought to be mediated by 5-HT2A receptors for which SB 200646A has its next highest affinity (50 fold less) after the 5-HT2C and 5-HT2B sites. 4. SB 200646A (20, 40 mg kg-1, p.o., 1 h pretest) also reversed mCPP (0.5 mg kg-1, i.p., 30 min pretest)-induced anxiety in the social interaction test, under low light familiar conditions. 5. When given alone, under high light unfamiliar conditions, SB 200646A (2-40 mg kg-1, p.o.) increased active social interaction without affecting locomotor activity in the rat social interaction test. This is consistent with an anxiolytic action of SB 200646A. 6. These results indicate that SB 200646A has in vivo efficacy and that 5-HT2C or 5-HT2B receptors are indeed likely to mediate mCPP-induced hypolocomotion, hypophagia and anxiogenesis. They also suggest that 5-HT2C,2B receptor blockade induces anxiolysis.

Animals↗
PubMed1994

Anxiety and drinking behavior: moderating effects of tension-reduction alcohol outcome expectancies.

We evaluated whether alcohol outcome expectancies moderate the association between measures of anxiety and alcohol use. Student subjects completed questionnaires related to their level of anxiety, recent alcohol-use patterns, and outcome expectancies for alcohol to be tension reducing. Interviews were used to determine the presence or absence of alcohol dependence in subjects and in their first- and second-degree relatives. Consistent with predictions, male subjects with high tension-reduction alcohol outcome expectancies showed a stronger positive correlation between measures of anxiety and drinking behavior than did male subjects with low tension-reduction outcome expectancies. However, this effect was not found for female subjects. We note past studies showing similar gender effects, and relate the overall study findings to the tension-reduction hypothesis of stress-induced drinking.

Adaptation, Psychological↗
PubMed1994

Alcohol norms, expectancies, and reasons for drinking and alcohol use in a U.S. versus a Japanese college sample.

Two hundred eighty-two students at Arizona State University in the U.S. and 339 students at Okayama University in Japan completed a questionnaire on their alcohol use, expectancies of the effects of alcohol on their own and others' moods and behaviors, the desirability of these effects, norms of significant others for levels of alcohol use and the subject's desire to comply with these norms, and reasons for drinking and not drinking alcohol. Although frequencies of current drinkers versus abstainers did not differ between the two samples, the U.S. students began regular alcohol use at a significantly earlier age, currently drank more alcohol, had higher alcohol expectancies for emotional responses, and endorsed more celebratory reasons for drinking than their Japanese counterparts. U.S. students, however, had lower expectancies for flushing and lower perceived norms for drinking. Hierarchical multiple regressions performed using data from the current drinkers indicated that expectancies of disinhibition and especially aggressiveness after alcohol use, alcohol norms, celebratory (but not pathological) reasons for drinking, and reasons for not drinking were more predictive of reported levels of alcohol use among the U.S. students as compared with the Japanese students.

Adolescent↗