PubMed · 3844903
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D R Andrews, C Taylor. 1985. Documenting post-anesthesia recovery.. https://pubmed.ncbi.nlm.nih.gov/3844903/
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To test the hypothesis that during augmented breaths the prolonged expiratory time is correlated with the activity of medullary post-inspiratory neurons, changes in diaphragm electromyogram and post-inspiratory neuronal activities were examined in pentobarbital anesthetized rats. During augmented breaths, the mean total expiratory time significantly increased (from 0.57 +/- 0.02 to 1.20 +/- 0.07 s, P < 0.01), but the mean duration of post-inspiratory inspiratory activity (PIIA) was significantly decreased (from 0.08 +/- 0.01 to 0.02 +/- 0.003 s, P < 0.01) compared to control breaths. The mean time which the diaphragm was electrically silent was observed to be significantly prolonged during augmented breaths (from 0.48 +/- 0.02 to 1.19 +/- 0.07 s, P < 0.01). During significant prolongations of expiratory time in augmented breaths, most of the recorded neurons (9/10) in the medulla showed sustained discharges. The mean duration of discharges was longer than that of PIIA (0.02 +/- 0.003 vs. 0.50 +/- 0.10 s, P < 0.01). The mean firing frequency/breath significantly increased compared to control breaths (9.45 +/- 1.69 vs. 37.6 +/- 7.13 imp/breath, P < 0.01). These results suggested that during augmented breaths, the prolonged expiratory period may not be mediated by persisting post-inspiratory neuronal activity in the medulla.
2-Aroyl-4-(omega-aminoacyl)- (4) and 4-aroyl-2-(omega-aminoacyl)pyrroles (9) represent a new, structurally novel class of anticonvulsant agents. Compounds of type 4 were prepared by Friedel-Crafts acylation of a 2-aroylpyrrole with an omega-chloroacyl chloride followed by displacement of the chloro group by a primary or secondary amine. Compounds of type 9 were prepared by Friedel-Crafts aroylation of a 2-(omega-chloroacyl)pyrrole followed by displacement by an amine. These compounds were active in the mouse and rat maximal electroshock tests but not in the mouse metrazole test. The lead compound, RWJ-37868, 2-(4-chlorobenzoyl)-4-(1-piperidinyl-acetyl)-1,3,5-trimethylpyrrole++ + (4d), showed potency and therapeutic index comparable to those of phenytoin and carbamazepine and greater than those of sodium valproate. This compound blocked bicuculline induced seizures, did not elevate seizure threshold following iv infusion of metrazole, and blocked influx of Ca2+ ions into cerebellar granule cells induced by K+ or veratridine.
(3 alpha,5 alpha)-3-Hydroxypregnan-20-ones and (3 alpha,5 alpha)-3-hydroxypregnane-11,20-diones bearing a 2 beta-morpholinyl substituent were synthesized, and the utility of these steroids as anesthetic agents was evaluated through determination of their potency and duration of hypnotic activity in mice after intravenous administration. Alkylation of the morpholinyl substituent or chlorination at C-21 afforded the novel amino steroids (2 beta,3 alpha,5 alpha)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)-pregnane-11,20-dione (19) and (2 beta,3 alpha,5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one (37) that were more potent and advantageously produced shorter sleep times than related compounds which were previously reported. Furthermore, salts of these and other amino steroids generally retained good aqueous solubility. In a radioligand binding assay the compounds inhibited the specific binding of [35S]-tert-butyl bicyclophosphorothionate to rat whole brain membranes, and in an electrophysiological assay they potentiated GABAA receptor-mediated currents recorded from voltage-clamped bovine chromaffin cells. These in vitro results are consistent with the anesthetic activity of the amino steroids being related to their modulatory effects at GABAA receptors.