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Biomedical subjects

D M Jackson

Publications and source records attributed to D M Jackson.

At least 73 records · Page 4Linked to original sources
PubMed1994

Dopamine receptor antagonists block amphetamine and phencyclidine-induced motor stimulation in rats.

d-Amphetamine (DEX) and phencyclidine (PCP) increased motor activity in rats as measured in automated activity cages. Analysis of the stimulation indicated that both drugs increased horizontal activity (total activity), locomotion, and peripheral activity. However, DEX increased while PCP decreased the incidence of rearing. The ability of different drugs to antagonise DEX- and PCP-induced increases in total activity (called stimulation) was measured. Dopamine (DA) D1 receptor antagonists (SCH23390, NNC-01-0112) were 7-8 times more potent in blocking DEX than PCP. DA D2 receptor antagonists (raclopride, remoxipride, haloperidol) were only 1-2 times more potent against DEX-induced stimulation. Nonselective DA receptor antagonists were also tested. Chlorpromazine was more potent against DEX than against PCP. Buspirone and sertindole were slightly more potent in blocking PCP than DEX. Ritanserin (5-HT2 receptor antagonist) was inactive against both stimulants. 8-OH-DPAT (5-HT1A receptor agonist) potentiated the stimulant effects of DEX and PCP. Prazosin (alpha 1-adrenergic receptor antagonist) partially blocked both DEX and PCP. Most drugs tested depressed spontaneous motor activity. Remoxipride and sertindole, however, caused very little depression even at doses several times higher than those needed to block DEX or PCP. The data show clear pharmacological differences between DEX- and PCP-induced stimulation.

Animals↗
PubMed1994

Dopamine receptors: molecular biology, biochemistry and behavioural aspects.

The description of new dopamine (DA) receptor subtypes, D1-(D1 and D5) and D2-like (D2A, D2B, D3, D4), has given an impetus to DA research. While selective agonists and antagonists are not generally available yet, the receptor distribution in the brain suggests that they could be new targets for drug development. Binding characteristics and second messenger coupling has been explored in cell lines expressing the new cloned receptors. The absence of selective ligands has meant that in vivo studies have lagged behind. However, progress has been made in understanding the function of DA-containing discrete brain nuclei and the functional consequence of the DA's interaction with other neurotransmitters. This review explores some of the latest advances in these various areas.

Amino Acid Sequence↗
PubMed1994

Preclinical findings with new antipsychotic agents: what makes them atypical?

Many early antipsychotics such as haloperidol, while effective in treating the symptoms of schizophrenia, cause detrimental side effects and moreover induce nonspecific sedation in many patients. Newer drugs such as remoxipride are as effective as the classical antipsychotics but induce fewer debilitating side effects. These clinical properties are reflected to some extent in their preclinical pharmacology, with drugs such as remoxipride having effects on various preclinical behavioural and biochemical models that are quite different to those exerted by drugs such as haloperidol. This article reports some new behavioural data and discusses the various mechanisms that can underlie the effect of new atypical antipsychotics.

Animals↗
PubMed1994

Combating pharmacist shortage through labor certification.

Several solutions, ranging from increased technician duties to salary raises, automation, and increasing job satisfaction, have been presented in the literature as methods of assuaging the pharmacist shortage. Although a significant portion of pharmacy graduates from American pharmacy colleges are foreign nationals, no marketing strategies have been elucidated in the retention and recruitment of foreign nationals through labor certification. Labor certifications are generally approved by the Secretary of Labor if the following factors have been verified: 1) there are not sufficient United States workers who are able, willing, qualified, and available for employment; and 2) the employment of the foreign national will not adversely affect the wages and working conditions of U.S. workers similarly employed. When properly understood, the labor certification process is a test of the job market where foreigners, by virtue of their skills and qualifications, attain certification which subsequently leads to permanent residency (green card). The objective of this report is to elucidate the tedious yet effective method of retaining American-educated foreign nationals through labor certification.

Documentation↗
PubMed1993

Binding characteristics of remoxipride and its metabolites to dopamine D2 and D3 receptors.

The substituted benzamide, remoxipride, is a new atypical antipsychotic agent with good clinical efficacy and low extrapyramidal side-effect potential. In the present study, the in vitro receptor binding properties of remoxipride and several of its metabolites to rat striatal dopamine D2 and cloned human dopamine D2A and D3 receptors were investigated. Remoxipride bound to [3H]raclopride-labelled dopamine D2 receptors in rat striatum with an affinity (Ki) of 113 nM. The significantly lower affinities of remoxipride reported when [3H]spiperone was used as a radioligand are suggested to be due to methodological problems associated with the use of very high-affinity radioligands. Some of the phenolic metabolites of remoxipride found mainly in rat exhibited considerably higher affinities to dopamine D2 and D3 receptors than remoxipride itself. The pyrrolidone metabolites found mainly in the human had very low dopamine D2 and D3 affinities. The present in vitro results suggest that the behavioural effects of remoxipride in rats may reflect the effect of remoxipride and some of its high-affinity metabolites.

Animals↗
PubMed1993

Comparison of conditioned taste aversions produced by MDMA and d-amphetamine.

Many drugs of abuse such as d-amphetamine support the development of taste aversion in a conditioned taste aversion paradigm. However, it has yet to be established whether methylenedioxymethamphetamine (MDMA), an amphetamine-like stimulant, has this property. A direct comparison was made between MDMA and d-amphetamine over a dose range of 0.125-2.0 mg/kg (SC). Two pairings of either drug with saccharin produced dose-related taste aversions to saccharin that were retained for at least three successive testing trials. The minimally effective dose was 1 mg/kg for MDMA and 0.5 mg/kg for d-amphetamine. The relative potency of MDMA to amphetamine was 4.5, similar to that previously reported for drug discrimination and self-stimulation.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Unique binding characteristics of antipsychotic agents interacting with human dopamine D2A, D2B, and D3 receptors.

In the present study we have compared the pharmacological properties of human dopamine (DA) D2A, D2B, and D3 receptors expressed in mammalian cell lines, using [3H]raclopride as a radioligand. Most of the compounds tested had about equal affinity for D2A and D3 receptors, with the exception of remoxipride, which displayed a 10-fold D2 selectivity, and the aminotetralin (+)-UH 232, which displayed a 5-fold D3 selectivity. Several antipsychotic agents, including clozapine and substituted benzamides, bound with 2-3-fold higher to the D2B (short) than to the D2A (long) isoform, whereas others failed to differentiate between the two isoforms. The atypical antipsychotic agent clozapine bound in a biphasic manner and with unexpectedly high affinity (35 nM) to the D2B receptor, suggesting that clozapine may not be as D4 selective as reported previously. In addition, remoxipride, a new antipsychotic agent with low potential to produce extrapyramidal side effects, displayed 2-3-fold higher affinity for the D2B receptor than for the D2A receptor. Furthermore, sodium differently regulated clozapine and benzamide binding to the various DA receptor subtypes. Thus, sodium decreased the affinity of clozapine for D2A and D2B receptors about 3-fold, whereas the affinity for D3 receptors was unaltered. In contrast, the affinity of raclopride for the three DA receptor subtypes was increased by sodium. Whether the unique characteristics of the binding of clozapine and benzamides to cloned DA receptors demonstrated in the present study are related to the favorable clinical properties of these compounds remains to be elucidated.

Animals↗
PubMed1992

The effect of nedocromil sodium on the isolated rabbit vagus nerve.

Nedocromil sodium depolarized the isolated rabbit vagus nerve. The depolarization was blocked by DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) and did not occur when the nerve was bathed in solutions low in chloride. After depolarization the nerve was refractory to nedocromil sodium for an hour. It is suggested that nedocromil sodium can affect a chloride channel.

Animals↗
PubMed1992

Cocaine facilitation of prefrontal cortex self-stimulation: a microstructural and pharmacological analysis.

A novel self-stimulation methodology involving a fixed-interval (FI-5 s) schedule of reinforcement, microanalysis and threshold evaluation was used to investigate the effects of cocaine on rats lever pressing for electrical stimulation of the prefrontal cortex. Cocaine (15 mg/kg) increased medial prefrontal cortex (MPC) self-stimulation rates under FI-5 by a mean of 269% and reduced current thresholds for self-stimulation. A similar facilitation was evident with self-stimulation of the sulcal prefrontal cortex. Microanalysis showed that cocaine decreased inter-response times and post-reinforcement pauses, increased responding in the second and third quartiles of the inter-reinforcement interval (IRI) and decreased responding in the fourth IRI quartile. Schedule control of responding was still evident following cocaine despite the profound facilitation of response rates. Increased response rates were seen up to 48 h following a single dose of cocaine, suggesting sensitization of the PFC reinforcement substrate. The acute effects of cocaine on MPC self-stimulation were completely reversed by the dopamine (DA) D1 antagonist SCH 23390 0.02 mg/kg) and the D2 antagonist raclopride (0.3 mg/kg) but not by naloxone (0.5 mg/kg). These results are consistent with previous studies demonstrating the PFC as part of the neural substrate mediating cocaine reward. Further, these results implicate DA receptors in the reinforcing properties of both cocaine and MPC self-stimulation.

Animals↗
PubMed1992

Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen-induced lung eosinophilia in guinea-pigs.

A close association has been recognized between activated T cells and eosinophils in asthma, albeit circumstantial. The present study attempted to investigate this relationship in an animal model of lung eosinophilia using the new generation of T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was assessed by bronchoalveolar lavage. All three agents caused a marked suppression of lung eosinophilia at 24 h post-challenge when the compounds were administered at the time of sensitization but not when administered for 3 days before lavage. However, the lung eosinophilia at 72 h post-challenge was reduced significantly by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were administered for 3 days, before lavage. These results strongly suggest the involvement of T cells in antigen-induced late phase (72 h) eosinophilia in guinea-pigs but not at 24 h. The effects of cyclophosphamide were always associated with a reduction in circulating white cell counts, whereas cyclosporin A and FK506 showed no myelotoxic properties. These results suggest the potential therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.

Animals↗
PubMed1992

Preferential stimulation of locomotor activity by ventral tegmental microinjections of (-)-nicotine.

In the present study the effect of acutely administered (-)-nicotine on locomotor activity was measured after direct bilateral microinjections into the nucleus accumbens (Acb) or into the ventral tegmental area (VTA) of rats. Intrategmental (-)-nicotine (either 0.02 or 2 micrograms/side) increased locomotor activity, the effect being greatest after the lower dose. The stimulation began almost immediately and was shortlasting with peak activity occurring at 30 min. After injection. Intra-accumbal (-)-nicotine (either 0.02, 2 or 20 micrograms/side) caused only a marginal short enhancement of activity which was not dose-dependent. The time course of enhanced activity was similar to that observed after intrategmental injection. Our results indicate that the nicotine-induced hyperlocomotion may arise primarily from activation of VTA nicotinic cholinoceptors (nAchRs), whereas activation of the accumbal nAchRs is less significant in regard to this effect.

Animals↗
PubMed1991

Correlation of amniotic fluid index and nonstress test in patients with preterm premature rupture of membranes.

The amniotic fluid index and the nonstress test are commonly used in the expectant management of preterm premature rupture of membranes. This study was designed to investigate the interrelationship of the nonstress test and the amniotic fluid index during the preterm rupture of membranes latency period. Fifty patients with preterm premature rupture of membranes for greater than 48 hours were prospectively followed with daily 1-hour nonstress tests and blinded, daily amniotic fluid index examinations (totaling 422 evaluations). The overall average daily amniotic fluid index was statistically lower in the earlier gestations and nulliparous patients but was not influenced by the fetal position or nonlaboring uterine activity. An increased incidence of variable decelerations and nonreactive nonstress tests was associated with a significantly lower overall average daily amniotic fluid index, but these differences were beyond the standard precision of the amniotic fluid index examination. The daily nonstress test appears to identify clinically significant lower fluid volumes during the latency period and should remain the mainstay in the management of preterm premature rupture of membranes.

Adult↗
PubMed1991

Role of dopamine and GABA in the control of motor activity elicited from the rat nucleus accumbens.

The application of 1.2 and 12.0 micrograms/side of the GABAA receptor agonist 3-aminopropane sulphonic acid bilaterally into the nucleus accumbens (Acb) of rats nonsignificantly depressed locomotor activity as assessed in automated Animex activity cages, while the highest dose (60 micrograms/side) significantly stimulated activity. The GABAA receptor antagonists picrotoxinin (0.0625 and 0.125 micrograms/saide) and bicuculline (0.895 micrograms/side) produced forward locomotion around the cage accompanied by a number of other behaviours. The GABAB agonist baclofen (0.023 and 0.092 micrograms/side) induced a short-lasting (18 min) locomotor depression. None of the GABAB antagonists tested (2-hydroxysaclofen 2.6 micrograms/side, two novel beta-(benzo[b]furan) analogues of baclofen 9G or 9H each 6.8 micrograms/side, 4-aminobutylphosphonic acid 1.32 micrograms/side and phaclofen 0.535 and 2 micrograms/side) significantly affected locomotor activity. In rats pretreated with reserpine and alpha-methyl-p-tyrosine, picrotoxinin (0.0625 and 0.125 micrograms/side) did not significantly alter locomotor activity. Furthermore, when picrotoxinin (0.0625 micrograms/side) was combined with either the selective dopamine (DA) D1 agonist SKF38393 or the selective D2 agonist quinpirole, no significant alteration in locomotor function occurred. When SKF38393 and quinpirole were coadministered, significant stimulation occurred which was further enhanced by the addition of picrotoxinin. It is concluded that GABAA receptors, together with D1 and D2 receptors, play a major role in modulating the control of motor function by the Acb of rats.

Animals↗
PubMed1991

Public awareness of the symptoms of diabetes mellitus.

A cross-sectional survey by standard questionnaire was conducted to determine the public's knowledge (n = 480) of diabetes and diabetes symptoms. Four hundred and sixty-two (96%) subjects had heard of diabetes, 350 (73%) could give a rudimentary definition of diabetes, but 231 (48%) were unable to name any symptom and only 20 (4%) knew of thirst and polyuria in combination. The public's knowledge of diabetes symptoms is poor. This may possibly contribute to delayed presentation of Type 2 diabetes.

Adult↗