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Biomedical subjects

F Murray

Publications and source records attributed to F Murray.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between changes in daily air pollution and hospitalizations in Perth, Australia 1992-1998: a case-crossover study.

A case-crossover study was undertaken to investigate the relationship between daily air pollutant concentrations and daily hospitalizations for selected disease categories in Perth, Western Australia. Daily measurements of particles (measured by nephelometry and PM2.5), photochemical oxidants (measured as ozone), nitrogen dioxide (NO2) and carbon monoxide (CO) concentrations were obtained from 1992 to 1998 via a metropolitan network of monitoring stations. Daily PM2.5 concentrations were estimated using monitored data, modelling and interpolation. Hospital morbidity data for respiratory, cardiovascular (CVD), gastrointestinal (GI) diseases, chronic obstructive pulmonary diseases (COPD) excluding asthma; pneumonia/influenza diseases; and asthma were obtained and categorized into all ages, less than 15 years and greater than 65 years. Gastrointestinal morbidity was used as a control disease. The data were analyzed using conditional logistic regression. The results showed a small number of significant associations for daily changes in particle concentrations, nitrogen dioxide and carbon monoxide for the respiratory diseases, CODP, pneumonia, asthma and CVD hospitalizations. Changes in ozone concentrations were not significantly associated with any disease outcomes. These data provide useful information on the potential health impacts of air pollution in an airshed with very low sulphur dioxide concentrations and lower nitrogen dioxide concentrations commonly found in many other cities.

Air Pollution↗
PubMed2005

Determination of guinea-pig cortical gamma-secretase activity ex vivo following the systemic administration of a gamma-secretase inhibitor.

(2S)-2-{[(3,5-Diflurophenyl)acetyl]amino}-N-[(3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]propanamide (compound E) is a gamma-secretase inhibitor capable of reducing amyloid beta-peptide (1-40) and amyloid beta-peptide (1-42) levels. In this study we investigated the effect of in vivo administration of compound E on guinea-pig plasma, CSF and cortical amyloid beta-peptide (1-40) concentration. Using repeated sampling of CSF, compound E (30 mg/kg p.o.) was shown to cause a time-dependent decrease in CSF amyloid beta-peptide (1-40) levels, which was maximal at 3 h (70% inhibition), compared to baseline controls. After 3 h administration, compound E (3, 10 and 30 mg/kg p.o.), reduced plasma, CSF and DEA-extracted cortical amyloid beta-peptide (1-40) levels by 95, 97 and 99%; 26, 48 and 78%; 32, 33, and 47%, respectively, compared to vehicle control values. In the same animals, compound E (3, 10 and 30 mg/kg p.o.) inhibited cortical gamma-secretase activity, determined ex vivo using the recombinant substrate C100Flag, by 40, 71 and 79% of controls, respectively. These data demonstrate the value of determining not only the extent by which systemic administration of a gamma-secretase inhibitor reduces amyloid beta-peptide, but also the inhibition of brain gamma-secretase activity, as a more direct estimate of enzyme occupancy.

Administration, Oral↗
PubMed2004

Autocatalyst-derived platinum, palladium and rhodium (PGE) in infiltration basin and wetland sediments receiving urban runoff.

The emission of platinum group elements (PGE) from automobile catalytic converters has led to rapid increases in Pt, Pd and Rh concentrations in roadside media. Significant quantities of the PGE may enter and accumulate in fluvial systems via road runoff. This paper examines the occurrence and spatial distribution of autocatalyst-derived PGE in surface sediments of infiltration basin and wetland sediments receiving road-runoff in Perth, Western Australia. Samples were analysed by ICP-MS following microwave digestion and cation exchange. PGE concentrations ranged between 1.5-17.2 Rh, 5.4-61.2 Pd and 9.0-103.8 ng g(-1) Pt. The highest levels of PGE were generally found at basin topographic low points and these concentrations were found to be strongly related to the area of road surface drained and the traffic volume. PGE ratios in infiltration basin and wetland sediments were within the typical range of catalytic converter compositions. However, comparisons of PGE ratios between parent road dusts and infiltration basin sediments revealed a systematic shift in Pt/Pd ratios, suggesting that PGE fractionation can occur during transport through the drainage system and that a small portion of Pd in road dust may be solubilised under natural conditions.

Australia↗
PubMed2003

Anthropogenic platinum group element (Pt, Pd and Rh) concentrations in road dusts and roadside soils from Perth, Western Australia.

The emission of platinum group elements (PGE) from automobile catalytic converters has led to rapid increases in Pt, Pd and Rh concentrations in roadside media. This article represents the first detailed study to assess PGE levels in road dusts and roadside soils in Australia. Road dust and roadside soil samples were analysed by ICP-MS following microwave digestion and cation exchange. All samples show elevation of PGE above average upper crust values, with maximum values of 420 ng g(-1) Pt, 440 ng g(-1) Pd and 91 ng g(-1) Rh. PGE ratios in road dusts and soils are consistent with known catalytic converter compositions and while Pt and Rh abundances are comparable with European studies, Pd levels are substantially higher in Australian samples. PGE in these samples are not correlated with Pb, though positive correlations with Ce, Cu and Y are evident. No straightforward relationship between traffic volume and PGE abundance is evident and factors such as driving style, topography, road drainage and potentially climate exert considerable influences.

Journal Article↗
PubMed2003

Comparison of Agrobacterium-mediated transformation of four barley cultivars using the GFP and GUS reporter genes.

Experiments were conducted to produce transgenic barley plants following infection of immature embryos with Agrobacterium tumefaciens. Transformed callus was obtained using hygromycin resistance as a selectable marker and either green fluorescent protein (GFP) or beta-glucuronidase (GUS) as a reporter. Significantly reduced plant transformation frequencies were obtained with the GFP gene compared to GUS. However, GFP proved to be an excellent reporter of early transformation events and was used to compare four barley cultivars for efficiency in two phases of transformation: the generation of stably transformed barley callus and the regeneration of plantlets from transformed callus. Transformed callus was generated at a high frequency (47-76%) in all four cultivars. Regeneration of transformed plantlets was also achieved for all four cultivars although the frequency was much higher for Golden Promise than for the other three genotypes, reiterating that genotype is an important determinant in the regenerative ability of barley. This study has demonstrated for the first time that Agrobacterium-mediated transformation can be used to transform the Australian cultivars Sloop and Chebec.

Agrobacterium tumefaciens↗
PubMed2003

Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results.

AIM: To compare the efficacy of esomeprazole, 20 mg once daily, vs. lansoprazole, 15 mg once daily, for the maintenance treatment of patients with healed reflux oesophagitis. METHODS: During the initial open healing phase, 1391 patients with endoscopically verified reflux oesophagitis and a history of heartburn, with or without acid regurgitation, received esomeprazole 40 mg for 4-8 weeks. Patients who were healed (identified by endoscopy at 4 or 8 weeks) and symptom free were then randomized to receive 6 months of treatment with esomeprazole, 20 mg once daily, or lansoprazole, 15 mg once daily. RESULTS: Esomeprazole, 20 mg once daily, maintained a significantly higher proportion of patients in remission than lansoprazole, 15 mg once daily, over 6 months [83% (95% CI, 80-86%) of esomeprazole recipients compared with 74% (95% CI, 70-78%) of lansoprazole recipients; P < 0.0001; life table estimates]. When data were analysed according to baseline Los Angeles grade classification, esomeprazole, 20 mg once daily, achieved consistently higher remission rates across all grades of disease severity, whereas the efficacy of lansoprazole decreased to a greater extent with increasing severity of reflux oesophagitis. CONCLUSION: Esomeprazole, 20 mg once daily, is more effective than lansoprazole, 15 mg once daily, in maintaining remission in patients with healed reflux oesophagitis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results.

INTRODUCTION: Esomeprazole, the first proton pump inhibitor to be developed as an optical isomer, has demonstrated more effective healing vs. omeprazole and lansoprazole in patients with reflux oesophagitis (RO). However, RO recurs in a high proportion (approximately 80%) of these patients within 12 months of initial therapy, highlighting the importance of maintenance treatment. Previous studies have shown esomeprazole to be effective as maintenance therapy in healed RO patients. AIM: This study was conducted to compare esomeprazole 20 mg once daily (o.d.) with lansoprazole 15 mg o.d. for the prevention of recurrence of RO. METHODS: 1391 patients with endoscopically verified RO (LA classification) were enrolled in this randomized, double-blind, parallel-group, multicentre trial. During the initial healing phase of the study, all patients received 4-8 weeks' open treatment with esomeprazole 40 mg: 1236 healed (identified by endoscopy at 4 and 8 weeks) and symptom-free (i.e. no heartburn or acid regurgitation) patients were randomized to 6 months' maintenance treatment with esomeprazole 20 mg o.d. or lansoprazole 15 mg o.d. Time to relapse (relapse of RO and/or discontinuation due to symptom recurrence) was analysed using a log-rank test. RESULTS: Esomeprazole maintained a significantly higher proportion of patients in remission than lansoprazole over the 6-month course of treatment (P < 0.0001, intention-to-treat analysis). After 6 months' treatment, 83% of esomeprazole recipients were in remission compared with 74% of lansoprazole recipients (life-table estimates). Esomeprazole gave a longer time to relapse than lansoprazole irrespective of baseline LA Grade, significantly so for baseline LA Grades B, C and D (P < 0.05 for each comparison). Significantly more patients were free from heartburn in the esomeprazole group compared with the lansoprazole group at 1, 3 and 6 months (P < 0.05). Significant differences at 6 months between esomeprazole 20 mg o.d. and lansoprazole 15 mg o.d. were also observed for control of epigastric pain and acid regurgitation (P < 0.05 and P < 0.001, respectively). Both treatment regimens were well tolerated. CONCLUSION: Esomeprazole 20 mg o.d. is a more effective maintenance treatment than lansoprazole 15 mg o.d. for symptom-free patients with healed RO.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Helicobacter Pylori eradication therapy: getting research into practice.

Helicobacter Pylori (H. Pylori) is the primary cause of duodenal ulcer (DU). Guidelines recommend that all patients with DU be considered for Helicobacter Pylori Eradication Therapy (HPET). However, the proportion of patients with DU on long term anti-ulcer medication receiving HPET is small. This study examined the effectiveness of the continuing medical education (CME) network of the Irish College of General Practitioners (ICGP) in promoting best practice in DU treatment among GPs in an eastern region of Ireland. Ninty eight GPs recruited from the CME network of the ICGP were randomised in two cohorts. Cohort 1 received an (early) intervention; GPs were asked to identify their patients with DU receiving long term anti-ulcer medication and prescribe HPET according to defined criteria. Cohort 2 received the intervention later. Prescribing of HPET was monitored using routine prescribing data. Twenty per cent (286/1,422) of patients in cohort 1 and 19.2% (127/661) in cohort 2 had a DU. After exclusions, 53% (152/286) in cohort 1 and 30.7% (39/127) in cohort 2, were eligible for HPET. A significantly higher proportion of patients in cohort 1 received HPET compared with cohort 2 during the early intervention period (13.8% vs 0.0%, p<0.05). Reasons for not prescribing HPET included concurrent illness in patients, failure to comply with treatment. Best practice guidelines on HPET treatment of DU can be successfully applied using CME networks. This model could be repeated in another therapeutic area where established research is not yet current practice.

Algorithms↗
PubMed2001

Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes.

Somatostatin-14 elicits negative inotropic and chronotropic actions in atrial myocardium. Less is known about the effects of somatostatin-14 in ventricular myocardium. The direct contractile effects of somatostatin-14 were assessed using ventricular cardiomyocytes isolated from the hearts of adult rats. Cells were stimulated at 0.5 Hz with CaCl2 (2 mM) under basal conditions and in the presence of the beta-adrenoceptor agonist, isoprenaline (1 nM), or the selective inhibitor of the transient outward current (Ito), 4-aminopyridine (500 microM). Somatostatin-14 did not alter basal contractile response but it did inhibit (IC50 = 13 nM) the response to isoprenaline (1 nM). In the presence of 4-aminopyridine (500 microM), somatostatin-14 stimulated a positive contractile response (EC50 = 118 fM) that was attenuated markedly by diltiazem (100 nM). These data indicate that somatostatin-14 exerts dual effects directly in rat ventricular cardiomyocytes: (1) a negative contractile effect, observed in the presence of isoprenaline (1 nM), coupled to activation of Ito; and (2) a previously unreported and very potent positive contractile effect, unmasked by 4-aminopyridine (500 microM), coupled to the influx of calcium ions via L-type calcium channels. The greater potency of somatostatin-14 for producing the positive contractile effect indicates that the peptide may exert a predominantly stimulatory influence on the resting contractility of ventricular myocardium in vivo, whereas the negative contractile effect, observed at much higher concentrations, could indicate that localized elevations in the concentration of the peptide may serve as a negative regulatory influence to limit the detrimental effects of excessive stimulation of cardiomyocyte contractility.

4-Aminopyridine↗
PubMed2001

Physiological and metabolic characteristics of elite tug of war athletes.

OBJECTIVE: To determine the aerobic power (VO(2)MAX), body composition, strength, muscular power, flexibility, and biochemical profile of an elite international squad of tug of war athletes. METHODS: Sixteen male competitors (mean (SEM) age 34 (2) years) were evaluated in a laboratory. For comparative purposes, data were analysed relative to normative data for our centre and to a group of 20 rugby forwards from the Irish international squad. RESULTS: The tug of war participants were lighter (83.6 (3.0) v 104.4 (1.8) kg, p<0.0001) and had less lean body mass (69.4 (2.1) v 86.2 (1.2) kg) than the rugby players and had lower than normal body fat (16.7 (0.9)%); all values are mean (SEM). Aerobic power measured during a treadmill test was 55.8 (1.6) ml/kg/min for the tug of war participants compared with 51.1 (1.4) ml/kg/min for the rugby forwards (p<0.03). A composite measure of strength derived from (sum of dominant and non-dominant grip strength and back strength)/lean body mass yielded a strength/mass ratio that was 32% greater (p<0.0001) for the tug of war group than the rugby group. Dynamic leg power was lower for the tug of war group than the rugby forwards (4659.8 (151.6) v 6198.2 (105) W respectively; p<0.0001). Leg flexibility was 25.4 (2.0) cm for the tug of war group. Back flexibility was 28.6 (1.4) cm which was lower (p<0.02) than the rugby forwards 34.2 (1.5) cm. Whereas blood chemistry and haematology were normal, packed cell volume, haemoglobin concentration, and erythrocyte volume were lower in the tug of war group than in the rugby players (p<0.05). All three haematological measures correlated with muscle mass (packed cell volume, r(2) = 0.37, p<0.0001; haemoglobin concentration, r(2) = 0.13, p<0.05; erythrocyte volume, r(2) = 0.21, p<0.01). CONCLUSIONS: The data indicate that international level tug of war participants have excellent strength and above average endurance relative to body size, but have relatively low explosive leg power and back flexibility. The data provide reference standards for the sport and may be useful for monitoring and evaluating current and future participants.

Adolescent↗
PubMed2000

Modulation of [3H]MK-801 binding to NMDA receptors in vivo and in vitro.

[3H]MK-801 binding in vivo was used to determine the occupancy of NMDA receptor ligands shown to allosterically modulate binding in vitro. ED(50) values (mg/kg) were obtained for the channel blockers (+)-5-methyl-10,11-dihydro-5,4-dibenzo[a,d]cyclohepten-5,10-imine maleate ((+)-MK-801, 0.2), 1-(1-phenylcyclohexyl)piperidine (phencyclidine, PCP, 1.7) and ketamine (4.4). Antagonists at the glutamate (DL-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (DL-CPP, 5.7)) and glycine site (7-Chloro-4-hydroxy-3-(3-phenoxy)-phenyl-2(H)quinolinone (L-701,324, 14.1), 3R(+)cis-4-methyl-pyrrollid-2-one (L-687,414, 15.1)) inhibited [3H]MK-801 binding in vivo to varying maximum levels (69%, 103% and 45%, respectively). NR2B subunit-selective compounds acting at the ifenprodil site inhibited [3H]MK-801 in vivo by a maximum of 52-72% and gave ED(50) values (mg/kg) of: (+/-)-(1S*, 2S*)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol ((+/-)CP-101,606), 1.9; (+/-)-(3R, 4S)-3-[4-(4-fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol ((+/-)CP-283,097), 1.8; (+/-)-(R*, S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propanol ((+/-)Ro 25-6981), 1.0; ifenprodil, 6.0. The glycine site agonist D-serine stimulated binding to 151% of control with an ED(50) of 1.7 mg/kg. Results show that [3H]MK-801 binding in vivo may be used to measure receptor occupancy of ligands acting not only within the ion channel but also at modulatory sites on the NMDA receptor complex.

Animals↗
PubMed2000

Characterisation of N-methyl-D-aspartate receptor-specific [(3)H]Ifenprodil binding to recombinant human NR1a/NR2B receptors compared with native receptors in rodent brain membranes.

We have performed [(3)H]ifenprodil binding experiments under NMDA receptor-specific assay conditions to provide the first detailed characterisation of the pharmacology of the ifenprodil site on NMDA NR1/NR2B receptors, using recombinant human NR1a/NR2B receptors stably expressed in L(tk-) cells, in comparison with rat cortex/hippocampus membranes. [(3)H]Ifenprodil bound to a single, saturable site on both human recombinant NR1a/NR2B receptors and native rat receptors with B:(max) values of 1.83 and 2.45 pmol/mg of protein, respectively, and K:(D) values of 33.5 and 24.8 nM:, respectively. The affinity of various ifenprodil site ligands-eliprodil, (R:(*), R:(*))-4-hydroxy-alpha-(4-hydroxyphenyl)-beta-methyl-4-pehnyl-1-pi per idineethanol [(+/-)-CP-101,606], cis-3-[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]-3, 4-dihydro-2H:-1-benzopyran-4,7-diol [(+/-)-CP-283,097], and (R:(*), S:(*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol [(+/-)-Ro 25-6981] was very similar for inhibition of [(3)H]ifenprodil binding to recombinant human NR1a/NR2B and native rat receptors, whereas allosteric inhibition of [(3)H]ifenprodil binding by polyamine site ligands (spermine, spermidine, and arcaine) showed approximately twofold lower affinity for recombinant receptors compared with native receptors. Glutamate site ligands were less effective at modulating [(3)H]ifenprodil binding to recombinant NR1a/NR2B receptors compared with native rat receptors. The NMDA receptor-specific [(3)H]ifenprodil binding conditions described were also applied to ex vivo experiments to determine the receptor occupancy of ifenprodil site ligands [ifenprodil, (+/-)-CP-101,606, (+/-)-CP-283,097, and (+/-)-Ro 25-6981] given systemically.

Allosteric Site↗
PubMed2000

Evaluation of total volatile organic compound emissions from adhesives based on chamber tests.

In 1997, Homeswest in western Australia and Murdoch University developed a project to construct low-allergen houses (LAHs) in a newly developed suburb. Before the construction of LAHs, all potential volatile organic compound (VOC) emission materials used in LAHs are required to be measured to ensure that they are low total VOC (TVOC) emission materials. This program was developed based on this purpose. In recent times, the number of complaints about indoor air pollution caused by VOCs has increased. A number of surveys of indoor VOCs have indicated that many indoor materials contribute to indoor air pollution. Although some studies have been conducted on the characteristics of VOC emissions from adhesives, most of them were focused on VOC emissions from floor adhesives. Few measurements of VOC emissions from adhesives used for wood, fabrics, and leather are available. Furthermore, most research on VOC emissions from adhesives has been done in countries with cool climates, where ventilation rates in the indoor environment are lower than those in Mediterranean climates, due to energy conservation. VOCs emitted from adhesives have not been sufficiently researched to prepare an emission inventory to predict indoor air quality and to determine both exposure levels for the Australian population and the most appropriate strategies to reduce exposure. An environmental test chamber with controlled temperature, relative humidity, and airflow rate was used to evaluate emissions of TVOCs from three adhesives used frequently in Australia. The quantity of TVOC emissions was measured by a gas chromatography/flame ionization detector. The primary VOCs emitted from each adhesive were detected by gas chromatography/mass spectrometry. The temporal change of TVOC concentrations emitted from each adhesive was tested. A double-exponential equation was then developed to evaluate the characteristics of TVOC emissions from these three adhesives. With this double-exponential model, the physical processes of TVOC emissions can be explained, and a variety of emission parameters can be calculated. These emission parameters could be used to estimate real indoor TVOC concentrations in Mediterranean climates.

Adhesives↗
PubMed1999

Novel selective compounds for the investigation of imidazoline receptors.

Over several years our group has sought to synthesize and identify selective ligands for imidazoline (I) receptors, in particular the I2 binding site. As a consequence, [3H]2-(2-benzofuranyl)-2-imidazoline (2BFI) has proved extremely useful for binding and autoradiographic studies. More recently we have synthesized a BU series of compounds and examined these for their affinities for both I1 and I2 binding sites. BU224 (2-(4,5-dihydroimidaz-2-yl)-quinoline) shows high affinity for I2 receptors with a Ki of 2.1 nM. BU226 (2-(4,5-dihydroimidaz-2-yl)-isoquinoline) demonstrated slightly higher affinity (Ki 1.4 nM) for I2 receptors, but overall BU224 displayed greater selectivity for I2 over I1 receptors (832-fold) than BU226 (380-fold). Both compounds showed low (microM) affinity for alpha 2-adrenoceptors. Given BU224's ability to cross the blood brain barrier, we predict that its in vivo effects are likely to be mediated via I2 receptors. Brain dialysis revealed BU224 to dose dependently (0-20 mg/kg i.p.) elevate basal noradrenaline in rat frontal cortex and basal dopamine in striatum. In a rat model of opiate withdrawal, behavioral studies showed that BU224 (10 mg/kg, s.c.) was able to reduce acute weight loss and diarrhea, but not the number of wet dog shakes associated with the withdrawal syndrome.

Animals↗
PubMed1998

Evaluation of a teaching aid for dental students.

A new teaching aid to assist undergraduate dental students to learn charting methods was developed. The aim of this study was to evaluate the effectiveness of the aid. Baseline charting tests were completed by 58 inexperienced clinical students at the start of a weekly half-day attachment at 3 community dental service (CDS) teaching clinics. These students were randomly assigned, in their tutor groups, to act as either test or control groups. The test group was actively taught charting with the new aid over their first 5-week attachment and control students were taught in the traditional way. Final charting tests were completed at the end of the attachments by all students and their results compared with baseline test results. The test group improved their mean scores from 20 out of a possible 50 marks at baseline to 36 at final test, a mean increase of 15 marks and an improvement of 71%. The control group scored a mean of 18 marks at baseline and improved this to 25, an increase of 7 marks, an improvement of 39%. It is concluded that the new teaching aid is more effective in assisting the students to learn charting than the traditional method.

Dental Records↗
PubMed1996

The behavioural and neurochemical profile of the putative dopamine D3 receptor agonist, (+)-PD 128907, in the rat.

The functional relevance of the dopamine D3 receptor is still unresolved, largely because of the absence of selective D3 receptor ligands. In the present study we have examined the in vivo profile of (+)-PD 128907, a potent and functionally selective D3 receptor agonist. Low doses of (+)-PD 128907 reduced spontaneous locomotor activity in the rat (ED50 = 13 +/- 3 micrograms/kg, s.c.) a response which was comparable with the non-selective D2,3 receptor agonist apomorphine (ED50 = 13 +/- 1.6 micrograms/kg, s.c.). In addition (+)-PD 128907 impaired prepulse inhibition of the acoustic startle response, with significant effects observed at doses of 30 micrograms/kg when appropriate prepulse intensities were used. Higher doses reversed gamma-butyrolactone-induced catecholamine synthesis (ED50 = 95 +/- 22 and 207 +/- 37 micrograms/kg in accumbens and striatum respectively) and induced yawning (100-300 micrograms/kg), penile grooming (30-1000 micrograms/kg) and sniffing (> or = 300 micrograms/kg) although doses 3- to 10-fold greater than apomorphine were required to produce maximal effects. In contrast to apomorphine, however, (+)-PD 128907 failed to induce intense stereotyped licking and biting in the rat. In view of the potency and selectivity of (+)-PD 128907 for the D3 receptor, a role in the control of locomotor activity is suggested. In addition, the observation that (+)-PD 128907 disrupts prepulse inhibition, a phenomenon which is also impaired in schizophrenic subjects, may indicate the pathological importance of this receptor subtype.

4-Butyrolactone↗