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Biomedical subjects

R G Hall

Publications and source records attributed to R G Hall.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis and structure-activity relationships of benzophenone hydrazone derivatives with insecticidal activity.

A broad range of benzophenone hydrazone derivatives was prepared and tested against selected chewing insect pests, allowing the analysis of structure-activity relationships. Good activity was found only when the aromatic rings were substituted at the 4-positions with an halogen atom and a triflate or perhaloalkoxy group. In contrast, a number of substituents on the hydrazone part led to active compounds, the best results being achieved with acyl-type substituents. The excellent laboratory and greenhouse activity of the best representatives was confirmed in semi-field trials against Spodoptera littoralis.

Animals↗
PubMed1995

Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists.

The antispastic agent and muscle relaxant baclofen 1 is a potent and selective agonist for bicuculline-insensitive GABAB receptors. For many years efforts to obtain superior GABAB agonists were unsuccessful. We describe the syntheses and biological properties of two new series of GABAB agonists, the best compounds of which are more potent than baclofen in vitro and in vivo. They were obtained by replacing the carboxylic acid group of GABA or baclofen derivatives with either the phosphinic acid or the methylphosphinic acid residue. Surprisingly, ethyl- and higher alkylphosphinic acid derivatives of GABA yielded novel GABAB antagonists, which are described in part 2 of this series. Structure-activity relationships of the novel GABAB agonists are discussed with respect to their affinities to GABAB receptors as well as to their effects in many functional tests in vitro and in vivo providing new muscle relaxant drugs with significantly improved side effect profiles.

Animals↗
PubMed1995

Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists.

In 1987, 25 years after the synthesis of the potent and selective GABAB agonist baclofen (1), Kerr et al. described the first GABAB antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABAB antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABAB antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABAB receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABAB antagonists interacted also with postsynaptic GABAB receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABAB antagonists showed also protective effects in various animal models of absence epilepsy.

Administration, Oral↗
PubMed1995

Level of functioning, severity of illness, and smoking status among chronic psychiatric patients.

It was hypothesized that chronic psychiatric patients who had quit smoking would be more functional and have lower Brief Psychiatric Rating Scale (BPRS) scores than those who continued to smoke. We interviewed 300 chronic psychiatric patients followed in the community. Fourteen percent were former smokers and nearly 11% had never smoked. Fifty-six percent of the sample were current smokers who had no intention of quitting, 13% were considering quitting, and 6% were seriously preparing to quit or had actually quit for a short period. When compared with current smokers, former smokers were more likely to live independently (p < .026) and less likely to have a drug or alcohol problem (p < .013). A random sample of current smokers were compared with former smokers on the BPRS. Former smokers had lower total BPRS scores (p < .03), and lower withdrawal/retardation subscale scores (p < .0058) than current smokers. We concluded that better functioning patients who smoked would be more likely to quit.

Adult↗
PubMed1990

CGP 35348: a centrally active blocker of GABAB receptors.

The biochemical, electrophysiological and pharmacological properties of the new GABAB receptor blocker CGP 35348 are described. In a variety of receptor binding assays CGP 35348 showed affinity for the GABAB receptor only. CGP 35348 had an IC50 of 34 microM at the GABAB receptor. The compound antagonized (100, 300, 1000 microM) the potentiating effect of L-baclofen on noradrenaline-induced stimulation of adenylate cyclase in rat cortex slices. In electrophysiological studies CGP 35348 (10, 100 microM) antagonized the effect of L-baclofen in the isolated rat spinal cord. In the hippocampal slice preparation CGP 35348 (10, 30, 100 microM) blocked the membrane hyperpolarization induced by D/L-baclofen (10 microM) and the late inhibitory postsynaptic potential. CGP 35348 appeared to be 10-30 times more potent than the GABAB receptor blocker phaclofen. Ionophoretic and behavioural experiments showed that GABAB receptors in the brain were blocked after i.p. administration of CGP 35348. This compound may be of considerable value in elucidating the roles of brain GABAB receptors.

Adenylyl Cyclase Inhibitors↗
PubMed1990

Age, pattern of consultation, and functional disability in elderly patients in one general practice.

OBJECTIVE: To examine how functional disability varies with sex, age, and other variables in patients aged 75 and over living in the community and to ascertain whether a statistical model derived from the variables in this population usefully predicted functional disability in another of similar age. DESIGN: Retrospective study of data collected by interview and by examination of medical records. SETTING: An urban general practice with five partners and a list of 15,000 patients, very few of whom belonged to ethnic minorities. PATIENTS: 775 Patients (252 men, 523 women) aged 75 and over living in the community between September 1985 and August 1986; 13 other patients considered to be unsuitable and 14 who declined an interview were excluded. Also 94 patients who became 75 or joined the practice after August 1986. MAIN OUTCOME MEASURE: The proportions of fit, partially disabled, and severely disabled (housebound) patients. RESULTS: 90 Men (35.7%) and 128 women (24.5%) were fit, and 27 men (10.7%) and 116 women (22.2%) were housebound; in all age groups women were significantly more likely to be disabled than men. A significant trend towards greater disability was shown with increasing age and, more noticeably, with pattern of consultation when patients were divided into three categories based on the number of times they had attended the surgery and been visited at home over about two years. Statistical models gave the forecast percentage of fit and severely disabled patients for each sex, age group, and pattern of consultation, and a simple scheme was derived to identify from information wholly contained in medical records most of those patients most prone to severe disability. The scheme was verified applying it to a population of 94 elderly patients in 1988-9. CONCLUSION: Sex, age, and pattern of consultation together provide a quick indication of elderly patients' tendency to severe disability, which can help in screening and in day to day consultations.

Age Factors↗
PubMed1990

3-Aminopropanephosphinic acid is a potent agonist at peripheral and central presynaptic GABAB receptors.

The actions of the GABA analog 3-aminopropanephosphinic acid (3-APA) were studied in the guinea-pig isolated ileal preparation and at synapses between cultured rat hippocampal neurons. Like the GABAB receptor agonist, baclofen, 3-APA inhibited the electrically evoked ileal twitch. The EC50 for 3-APA was 0.8 microM; the EC50 for baclofen was 9 microM. In addition, the depressant responses to 3-APA and baclofen were blocked by the GABAB receptor antagonists phaclofen, saclofen, 2-hydroxy-saclofen and delta-aminovaleric acid. 3-APA also mimicked the presynaptic action of baclofen at GABAergic synapses between embryonic rat hippocampal neurons in culture. 3-APA reduced the amplitude of inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) by greater than 50% at a concentration of 1 microM, while baclofen reduced synaptic transmission to a similar degree at 10 microM. 3-APA did not alter membrane conductance, nor did the drug alter postsynaptic responses to GABA. These data show that 3-APA is a potent agonist at presynaptic GABAB receptors in the periphery and on GABAergic neurons from the central nervous system. The activity of 3-APA at central postsynaptic GABAB receptors remains to be studied.

Amino Acids↗
PubMed1990

Differing actions of baclofen and 3-amino-propylphosphinic acid in rat neocortical slices.

Rat neocortical slices maintained in Mg2(+)-free Krebs medium developed spontaneous paroxysmal discharges which were attenuated or suppressed by the gamma-aminobutyric acid-B (GABAB) receptor agonist baclofen, occasionally accompanied by a slight hyperpolarisation, and antagonised by the specific GABAB-receptor antagonist, 2-OH-saclofen. Over the same dose range, the GABA-analogue 3-amino-propylphosphinic acid (3-APA) caused a marked, prompt hyperpolarisation with little or no effect on the frequency of the discharges, although their amplitude was attenuated. In the presence of 2-OH-saclofen, 3-APA still induced a hyperpolarisation but the amplitude of the discharges was no longer affected. This marked difference in action between baclofen and 3-APA in the rat neocortical slices suggests there may be a heterogeneity of GABAB-receptors.

Animals↗
PubMed1988

GABAA and GABAB receptors in locus coeruleus: effects of blockers.

Racemic baclofen, (-)-baclofen and muscimol depressed all spontaneously firing locus coeruleus neurons tested in a slice preparation. Racemic phaclofen (100 microM; 1 mM) moderately antagonized the effects of racemic baclofen without antagonizing those of muscimol. Bicuculline (10, 30, 100 microM) potently antagonized the action of muscimol without affecting the inhibition of baclofen. Phaclofen and bicuculline had no pronounced effect on the spontaneous discharge rate of cells. The results suggests that there are GABAA and GABAB receptors in the locus coeruleus.

Animals↗
PubMed1987

Drugs, insecticides and other agents from Artemisia.

Essential oils from Artemisia (wormwood) are of botanical and pharmaceutical interest. They are used in traditional remedies in many parts of the world. In pure form the oil is a narcotic poison. Nearly all species are intensively bitter and strongly aromatic. Extracted substances from the plant have an antibacterial action and some of these substances have potential use in mosquito control. Other properties include toxicity to nematodes and inhibition of seedling growth of. Several chemical compounds have been isolated and identified.

Anthelmintics↗
PubMed1985

Inflammatory aneurysms of the abdominal aorta.

Over a 5 year period 268 abdominal aortic aneurysms were operated on, 15 of these (5.6%) showed the characteristic features of inflammatory aneurysms. Rupture of the aneurysm was an unusual method for presentation (one patient), and back and abdominal pain were present in 13 patients. The ESR may be of value in the pre-operative diagnosis. Ultrasound and CT scanning can, by the detection of a peri-aortic mass lead to confusion in the diagnosis. Two patients were initially diagnosed as having lymphoma. Strict adherence to the surgical principles outlined resulted in no mortality or significant morbidity in these 15 patients.

Aged↗
PubMed1985

Vein, Gore-tex or a composite graft for femoropopliteal bypass.

Experience with a variety of graft materials has suggested that the nature of the material significantly affects long term graft patency. In 126 femoropopliteal bypass grafts performed during a 54 month period, the over-all patency rate for RSV (68.0 per cent at three years) was significantly superior to either Gore-tex alone (34.1 per cent at three years) or a composite graft of RSV below the knee anastomosed to Gore-tex above the knee (49.3 per cent at three years). The composite graft performed significantly better than Gore-tex alone, however, in patients with poor runoff or when a distal anastomosis was performed below the knee. The reason for the superior performance of RSV or the composite over Gore-tex alone probably relates to compliance mismatch at the site of the distal anastomosis. While RSV remains the graft material of choice for femoropopliteal bypass grafting, a extensive role exists for the use of a composite graft rather than Gore-tex graft alone especially in patients with poor runoff with an anastomosis below the knee.

Aged↗
PubMed1981

Effects of orally administered activated charcoal on intestinal gas.

The effectiveness of activated charcoal in treating intestinal gas, following a gas producing meal, was compared with a placebo. Both the number of flatus events and breath hydrogen levels were measured. These experiments showed that orally administered activated charcoal was effective in preventing the large increase in the number of flatus events and increased breath hydrogen concentrations that normally occur following a gas-producing meal.

Administration, Oral↗