A study of air pollutants and acute asthma exacerbations in urban areas: status report.

A study to try to better understand the interactions between various air contaminants and acute asthma exacerbations is described. The study evaluates temporal associations between a panel of air contaminants and acute asthmatic exacerbations as measured by emergency room visits for asthma in communities in the Bronx and Manhattan in New York City (NYC). In addition, ambient levels of various air pollutants in two NYC communities are being compared.

The public health surveillance of asthma.

Asthma is a highly prevalent disease that affects the quality of life of many people in the United States. Yet there is limited descriptive epidemiological understanding of the disease, particularly at the state and local levels. Minimal surveillance of asthma is occurring across the country.

WIN 63480, a hydrophilic TCP-site ligand, has reduced agonist-independent NMDA ion channel access compared to MK-801 and phencyclidine.

NMDA channel blockers are potentially advantageous therapeutic agents for the treatment of ischemia and head trauma, which greatly elevate extracellular glutamate, because they should most effectively inhibit high levels of receptor activation. A novel high affinity TCP site ligand, WIN 63480, does not produce MK-801- or PCP-like behavioral activation at anti-ischemic doses. While WIN 63480, MK-801 and PCP were all observed to be effective blockers of open NMDA channels, WIN 63480 had much less access to closed NMDA channels.

Discovery of 6,11-ethano-12,12-diaryl-6,11-dihydrobenzo[b]quinolizinium cations, a novel class of N-methyl-D-aspartate antagonists.

6,11-Ethano-12,12-diaryl-6,11-dihydrobenzo[b]quinolizinium cations 8, a novel class of N-methyl-D-aspartate (NMDA) antagonists acting at the phencyclidine site, have been identified. Structure-activity relationship studies around the lead compound 8a led to the identification of 12g (WIN 67870-2), one of the most potent compounds in this series. Compound 12g has a Ki = 1.

Pharmacologic reversal of acute changes in diffusion-weighted magnetic resonance imaging in focal cerebral ischemia.

Recently, diffusion-weighted magnetic resonance imaging (DWI) has been shown to visualize acute ischemic lesions in the brain before changes are observable with conventional magnetic resonance imaging. However, the underlying mechanisms of these acute DWI changes are unclear and may include both reversible and irreversible damage. In this study, we demonstrate that acute DWI lesions may be reversed with MK801 therapy postischemia.

Sigma receptor binding affinity and inhibition of apomorphine-induced climbing.

Several relatively selective compounds with affinity for the sigma binding site were assessed for their ability to inhibit apomorphine-induced climbing in the mouse. Although, the majority of compounds inhibited apomorphine-induced climbing, there was no correlation between the ability to inhibit climbing and potency in sigma binding assays using [3H]1,3-di-o-tolylguanidine (DTG) or [3H](+)-pentazocine as ligands. The potency of the compounds to inhibit binding to muscarinic M1 or M2 receptors correlated with the potency to inhibit apomorphine-induced climbing.

In vivo assessment of napamezole, an alpha-2 adrenoceptor antagonist and monoamine re-uptake inhibitor.

Napamezole is an alpha-2 adrenergic receptor antagonist and a selective inhibitor of 5-hydroxytryptamine re-uptake in vitro. In the present study, napamezole was evaluated in vivo for its ability to antagonize alpha-2 adrenergic receptors and to inhibit 5-hydroxytryptamine re-uptake. The alpha-2 blocking activity of napamezole was demonstrated by its ability to: 1) antagonize clonidine-induced antinociception in mice (ED50 value, 36 mg/kg p.

Behavioral effects of neurotensin: operant responding and assessment of 'anhedonia'.

Neurotensin and antipsychotic drugs share certain properties. This study investigates whether neurotensin and neuroleptics share the ability to produce 'anhedonia'. A dose-response curve for the effect of neurotensin on continuously reinforced behavior was obtained in Experiment 1.

Evaluation of adenosine agonists as potential analgesics.

Adenosine agonists, N6-cyclohexyladenosine (CHA), N6-cyclopentyladenosine (CPA), N6-phenylisopropyladenosine (PIA), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-N-methylcarboxamidoadenosine (MECA) and 2-chloroadenosine (CADO), produced a dose-related inhibition of acetylcholine (ACh)-induced writhing in mice. The antinociceptive potency of adenosine agonists was comparable to that of morphine. Adenosine agonists were 10-1000 times more potent when given i.

Pharmacologic profile of fezolamine fumarate: a nontricyclic antidepressant in animal models.

Fezolamine [N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine-(E)-2- butenedioate] is a new, nontricyclic agent under investigation as a potential antidepressant. In vitro, it was 3 to 4 times more selective in blocking synaptosomal uptake of [3H]norepinephrine than uptake of [3H]serotonin or [3H]dopamine. In classical behavioral tests using monoamine-depleted animals, it prevented the depressant effects of reserpine and tetrabenzine.

Alpha 2-adrenergic agonists/antagonists: the synthesis and structure-activity relationships of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines.

The synthesis and alpha 2-adrenergic activity of a series of indolin-2-yl and tetrahydroquinolin-2-yl imidazolines are described. The indolin-2-yl imidazoline 4b was found to possess potent alpha 2-adrenergic agonist and antagonist activity. The modification of the substituents on the indoline ring of 4b has led to the separation of these activities.

Synthesis and antidepressant properties of novel 2-substituted 4,5-dihydro-1H-imidazole derivatives.

A unique combination of alpha 2-adrenoreceptor antagonist and serotonin-selective reuptake inhibitory activities has been identified in a series of 2-substituted 4,5-dihydro-1H-imidazole derivatives. This combination of blocking activities has provided one of these derivatives, napamezole hydrochloride (2), with potential as an antidepressant. A discussion of the syntheses of these compounds includes a convenient method for the conversion of nitriles to imidazolines with ethylenediamine and trimethylaluminum.

Two tests in rats for antianxiety effect of clinically anxiety attenuating antidepressants.

The effects of mianserin, trazodone, amoxapine, maprotiline, and doxepin were assessed in punishment and pentylenetetrazol drug discrimination paradigms. These two procedures are used to identify antianxiety activity in rats. In the punishment procedure, misanserin produced an inverse dose-related increase in punished responding.

Alpha 2-adrenergic antagonists effect on amphetamine-induced behaviors.

The effects of alpha 2-adrenergic antagonists on amphetamine-induced locomotion and stereotypy were studied in mice. Six alpha 2-antagonists (i.e.

Adaptation to cold antagonizes neurotensin-induced hypothermia in mice.

Intracerebrally-administered neurotensin produces a marked hypothermia in a variety of mammals. In this study, prior adaptation to a cold environment was found to significantly antagonize the hypothermia produced by intracisternally-administered neurotensin in mice. This antagonism required both previous exposure to cold ambient temperatures and cold exposure immediately prior to, or simultaneously with, neurotensin administration.

Determination of antinociceptive efficacy of drugs in mice using different water temperatures in a tail-immersion test.

A variety of analgesic drugs were tested for their ability to alter the response to noxious stimuli of differing severity in an attempt to develop a procedure to evaluate differences in efficacy of different analgesics. The severity of a noxious stimuli delivered to mice was varied by immersing the mouse tails in water maintained at 45, 50, 55 degrees C. As has been previously observed, the opiate analgesics morphine and nalorphine were active at all temperatures.

Pharmacological analysis of alpha-2 adrenergic mechanisms in nociception and ataxia.

In order to assess the involvement of alpha-2 adrenergic receptors in nociception, the in vitro potencies of seven alpha-2 adrenergic agonists (clonidine, guanabenz, guanfacine, BHT-920, ICI 106270, xylazine and lofexidine) were compared with their ability to prevent the writhing response elicited by i.p. administration of phenyl-p-guinone.

The effects of serotonin antagonists in a behavioral despair procedure in mice.

Six serotonin antagonists (pizotifen, mianserin, cyproheptadine, ketanserin, trazodone and methysergide) were tested in mice in a behavioral despair procedure. The behavioral despair procedure detects most antidepressant compounds. Pizotifen, mianserin and cyproheptadine were found to be active and the others were inactive.

Interactions of neurotensin with brain dopamine systems: biochemical and behavioral studies.

Intracisternal (i.c.) injection of neurotensin (NT) to rats or mice attenuated the locomotor hyperactivity induced by d-amphetamine, methylphenidate or cocaine, but not the increased activity induced by apomorphine or lergotrile.

The effects of chronic morphine treatment on neurotensin-induced antinociception.

Previous studies have shown that the opioid antagonist naloxone does not alter neurotensin (NT)-induced antinociception. In the present studies, tolerance to morphine in mice significantly attenuated NT-induced antinociception, but not NT-induced hypothermia. In addition, centrally administered NT inhibited naloxone-precipitated jumping in morphine-dependent mice.

The effects of neurotensin, beta-endorphin, and bombesin on ethanol-induced behaviors in mice.

The effects of the three peptides neurotensin, beta-endorphin, and bombesin on ethanol-induced behaviors were studied in mice. Intracisternal administration of these peptides to mice prolonged the duration of sleep induced by ethanol (5.2 g/kg).

The effect of neurotensin on food consumption in the rat.

The effect of neurotensin on feeding behavior were studied in rats. Intracerebroventricular administration of neurotensin (3.3-30 micrograms) produced a dose-related decrease in food intake in 24 h food deprived rats.

The effects of neuropeptides on discrete-trial conditioned avoidance responding.

The effects of intracerebroventricular administration of several peptides on discrete-trial, conditioned avoidance responding were assessed in the rat. Three peptides (neurotensin, bombesin and beta-endorphin) produced a neuroleptic-like effect (i.e.