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At least 19 recordsLinked to original sources
PubMed1976

Acute toxicity of bicyclic phosphorus esters.

The acute toxicity of 4-ethyl-1-phospha-2,6,7-trioxabicyclo (2.2.2) octane-1-oxide and 4-ethyl-1-phospha-2,6,7-trioxabicyclo (2.2.2) octane has been determined by different routes of application in various species of animals. The compounds stimulate the activity of the central nervous system and are highly toxic. They showed no toxic cumulative effects. The presence of the bicyclic phosphate ester in the combustion products of specific rigid polyurethane foams is discussed. The question is raised whether there may be an additional hazard caused by this combustion product in a real fire situation.

Aerosols↗
PubMed1979

Effects of propoxyphene, ethoheptazine, and azabicyclane on schedule-controlled responding: attenuation by pentobarbital but not naloxone.

The effects of propoxyphene, ethoheptazine, and azabicyclane, alone and in combination with 1 mg/kg naloxone, were studied in pigeons responding under a multiple fixed ratio, fixed interval schedule of food presentation. Low doses of pentobarbital (3, 5.6, and 10 mg/kg) attenuated the rate-decreasing effects produced by 20 mg/kg propoxyphene, ethoheptazine, and azabicyclane. Naloxone antagonized the rate-decreasing effects produced by 10 mg/kg azabicyclane but did not antagonize the rate-decreasing effects of propoxyphene or ethoheptazine.

Analgesics, Opioid↗
PubMedDate not supplied

Comparison of lindane, bicyclophosphate and picrotoxin binding to the putative chloride channel sites in rat brain and Torpedo electric organ.

The relative potencies of lindane, picrotoxin and several bicyclophosphate derivatives were compared in their ability to compete with 35S-t-butylbicyclophosphorothionate (35S-TBPS) binding sites in membranes derived from Torpedo electric organ and rat brain. Lindane proved to be ten times more potent in competing with 35S-TBPS binding in electric organ than rat brain, while the bicyclophosphate analogs displayed up to three orders of magnitude greater affinity for rat brain over electric organ. GABA inhibited 35S-TBPS binding in rat brain with moderate potency (IC50 = 30 microM), while unlabelled TBPS inhibited the binding of 3H-muscimol to the GABA receptor with an IC50 greater than 100 microM. The GABA receptor antagonist bicuculline increased 35S-TBPS binding in rat brain both in the presence and absence of 30 microM GABA. The results of the study are discussed in the context of a pharmacological discrimination between voltage-sensitive and receptor-gated Cl- channels in nervous tissue, with lindane and the i-propylbicyclophosphate derivative being the most selective compounds for discriminating between them.

Animals↗
PubMed1990

Synthesis of a new class of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives as highly potent 5-HT3 receptor antagonists.

A series of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid esters and amides containing a basic azacyclo- or azabicycloalkyl moiety has been synthesized and evaluated for 5-HT3 antagonistic activity in a radioligand binding assay ([3H]ICS 205930) and in the 5-HT-induced von Bezold-Jarisch reflex in the rat. It was found that endo-substituted azabicycloalkyl derivatives (e.g. 7a, 12a, 12b) were much more active than the corresponding exo analogues (e.g. 7b, 12h, 12i) or azacycloalkyl compounds. Amidic derivatives 12a, 12b, 12c, 12e, 13b, and 13c proved to be about 10 times more active than the corresponding ester derivatives 7a, 11a, 7c, 7d, 8a, and 8b. In particular, compound 12a (DA 6215) showed a Ki = 3.8 nM in the binding test and an ED50 = 1 nM/kg iv in the von Bezold-Jarisch reflex assay, an activity comparable to that of the reference compound 2 (ICS 205930, Ki = 2 nM, ED50 = 2.1 nM/kg). IR spectroscopy studies in the solid state and in CHCl3 solution revealed the existence of an intramolecular hydrogen bond in 13b, taken as a model compound for this class of substances. A molecular modeling study showed that 12a, in its internal hydrogen-bound conformation, well matches a recently proposed pharmacophoric model for 5-HT3 antagonist activity.

Animals↗
PubMed1976

7-Aza analogs of the analgetic agent azabicyclane. Synthesis and pharmacologic analysis.

Three 3,7-diazabicyclo[3.3.1]nonane derivatives (4) with a structural similarity to the analgetic agent azabicyclane (1) were prepared. The amino alcohol 4a was found to prefer a conformation wherein the six-membered ring to which the hydroxyl group is syn is in the boat form. These three compounds had increased basicity in comparison with 1 due to various forces stabilizing their monocationic states. Compounds 4a-c did not show analgetic activity at the dose levels tested.

Analgesics↗
PubMed1990

Sequential extraction--spectrofluorometric determination of lead and cadmium using cryptands.

A spectrofluorimetric method for the determination of ultratrace amounts of lead and cadmium is described based on the sequential extraction of the ternary ion-association complexes formed between the cation, a cryptand as the ligand and eosin as a counter ion. A linear working range from the detection limit (0.5 ng ml(-1) to 250 ng ml(-1) of lead and to 1 50 ng ml(-1) of cadmium was obtained. The relative standard deviation was 2-4%. The proposed method has been applied successfully to the determination of lead and cadmium in zinc metals and soft drinks.

Bridged Bicyclo Compounds↗
PubMed1976

Influence of a new antiulcer agent, ammonium 7-oxobicyclo (2, 2, 1) hept-5-ene-3-carbamoyl-2-carboxylate (KF-392) on gastric lesions and gastric mucosal barrier in rats.

Antiulcer effects of KF-392 were studied in several experimental gastric ulcer models in rats. It was found that KF-392 given orally at 1.0 to 5.0 mg/kg had a marked suppression on the developments of Shay ulcer as well as the aspirin-, stress-, and reserpine-induced gastric lesions. The influence of KF-392 on gastric mucosal barrier was also studied. A back diffusion of H+ into the gastric mucosa and a fall of transmucosal potential difference were induced with KF-392 given orally at the above mentioned doses. KF-392 given s.c. at 5.0 mg/kg showed no inhibition of Shay ulcer and no induction of back diffusion of H+ into the gastric mucosa.

Animals↗
PubMed1990

Activation and blockade of the acetylcholine receptor-ion channel by the agonists (+)-anatoxin-a, the N-methyl derivative and the enantiomer.

The effects of (+)- and (-)-anatoxin-a (AnTX) and N-methylanatoxin (M-AnTX) on peripheral nicotinic ion channel activity were studied using high micromolar concentrations. Whereas (+)-AnTX is an effective agonist at nanomolar concentrations, (-)-AnTX and M-AnTX were effective at low micromolar concentrations. The binding of [3H]perhydrohistrionicotoxin to the nicotinic acetylcholine receptor-ion channel was stimulated by the above agonist concentrations, but [3H]perhydrohistrionicotoxin binding was inhibited at high micromolar concentrations of each of the toxins. In single channel recordings, these toxins exhibited ion channel blocking properties; the concentration- and voltage-dependent kinetics of each were essentially the same. In the case of (+)-AnTX, desensitization was also present at micromolar concentrations. These data show that ion channel blockade may be a property of many anatoxin-a analogs, and that in the particular case of analogs with low agonist potency, ion channel blockade may be a concomitant primary effect of the toxins. Stereospecificity and number of amine moieties did not influence the ion channel blocking characteristics in this series of molecules, although these factors strongly modified agonist potency.

Amphibian Venoms↗
PubMed1990

The action of stress and anxiolytic and anxiogenic benzodiazepine receptors ligands on [35S] T-butylbicyclophosphorothionate binding in the rat cerebral cortex.

The effect of foot shock stress on [35S] t-butylbicyclophosphorothionate (TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of positive and negative modulators of the GABAergic transmission. 35S-TBPS binding was increased (30%) in cerebral cortex of rats exposed to foot shock compared to the non stressed rats. In contrast, the in vitro addition and the in vivo administration of anxiolytic and positive modulators of the GABAergic transmission inhibited the specific binding of 35S-TBPS. On the other hand, the anxiogenic beta-carbolines DMCM, beta CCM, FG 7142 and beta CCE mimicked in vivo and in vitro the effect of stress. The demonstration that stress, similar to anxiogenic beta-carbolines and opposite to benzodiazepines and anxiolytic beta-carbolines, increases 35S-TBPS binding in the rat cerebral cortex, suggests that some emotional state related to stress and anxiety may result from a diminished GABAergic transmission at the level of the GABA/benzodiazepine receptor/chloride ionophore complex.

Animals↗
PubMed1979

Analgesic properties of dezocine for relief of postoperative pain.

In a population of 61 surgical patients, 10 and 15 mg dezocine were compared with meperidine 100 mg for relief of postoperative pain. Pain relief experienced by the patient and pain intensity evaluated by a nurse and a physician displayed similar characteristics: dezocine 10 mg was less effective than meperidine but dezocine 15 mg showed a rapid onset of analgesic effect with a longlasting analgesia superior to meperidine. Vital signs remained stable within satisfactory limits with no respiratory depression occurring. Blood-gas analysis showed a significant but comparable increase in PaCO2 with slight decrease of PaO2 in all patients treated with dezocine or meperidine. Side effects observed included an overt sedative effect of both analgesics, which for dezocine appeared to be dose-related.

Adolescent↗
PubMed1992

Structure and molecular modeling of GABAA receptor antagonists.

The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts were made to identify in each structure the functional groups that are involved in receptor recognition and binding. A molecular modeling study revealed that (a) all compounds possess accessible cationic and anionic sites separated by an 4.6-5.2 A intercharge distance, (b) the antagonistic nature of the compounds can be explained by the presence of additional binding sites, (c) the correct spatial orientation of the additional binding sites is crucial for GABAA selectivity, and (d) the criteria determining the potency of the antagonist effect are an accurate intercharge distance (greater than 5 A) and the existence of hydrogen-bonding functionalities on one of the additional ring system. The presented pharmacophore accounts also for the inactivity of closely related compounds such as (-)-bicuculline, adlumidine, virosecurinine, allosecurinine, and the 4,6-diphenyl analogue of gabazine.

Alkaloids↗
PubMed1992

[Total synthesis of securinine].

Securinine, an alkaloid having strychnine-like action was synthesized using 1,4-cyclohexanedione as the starting material through the following sequence of reactions: condensation with piperidine, reduction, cyclization catalyzed by mercuric acetate and intramolecular condensation, totally in eleven steps. The IR, 1HNMR and melting point of the synthetic product is identical with those of natural securinine.

Alkaloids↗