The effect of a benzodiazepine, flurazepam, on the response of in vitro skeletal muscle preparations to muscle relaxants: are purines or their receptors involved?

1982 ◽  
Vol 60 (7) ◽  
pp. 877-884 ◽  
Author(s):  
John T. Hamilton ◽  
Peggy A. Stone
Keyword(s):  
Skeletal Muscle ◽  
Phrenic Nerve ◽  
Neuromuscular Blocking ◽  
Muscle Relaxants ◽  
Water Soluble ◽  
Neuromuscular Activity ◽  
Changing Trends ◽  
Low Concentrations ◽  
Partial Blockade

Changing trends in the use of anxiolytic agents and recent reassessment of their neuropharmacological activity has prompted this evaluation of the peripheral neuromuscular activity of the benzodiazepine, flurazepam. In previous reports we have documented peripheral neuromuscular activity of chlordiazepoxide and diazepam on the rat phrenic nerve diaphragm preparation. The water soluble benzodiazepine, flurazepam, has been studied on the rat phrenic nerve diaphragm and frog rectus abdominis in vitro. On the former preparation flurazepam enhanced and then blocked the response to indirect electrical stimulation (0.2 Hz) and readily blocked posttetanic potentiation and prevented the preparation from sustaining a tetanic contracture (30 Hz). On the later preparation, flurazepam blocked in a noncompetitive manner the response of the frog muscle to applied cholinergic agonists. Studies on the rat preparation with the neuromuscular blocking drug succinylcholine have shown an unexpected protection against blockade in preparations pretreated with low concentrations of flurazepam. This was not observed when flurazepam was given prior to d-tubocurarinc. The application of adenosine to rat diaphragms during steady-state partial blockade caused by flurazepam or d-tubocurarine showed an inhibiting action of adenosine which was reversed by theophylline. Pretreatment of rat preparations with dipyridamole significantly enhanced the blocking action of standard concentrations of succinylcholine.These results, along with those in the literature, encourage a reassessment of the action of purines and benzodiazepines on skeletal muscle and encourage a consideration of a possible involvement of purinergic neuromodulation of transmission which is unmasked when the safety factor for transmission is altered by muscle relaxants. The possible clinical significance of protection against succinylcholine by benzodiazepines is noted.

Steroid effects on permeability of rat thymic lymphocytes to α-aminoisobutyrate

1963 ◽  
Vol 205 (3) ◽  
pp. 446-452 ◽  
Author(s):  
Melvin Blecher
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Fluid ◽  
In Vivo Studies ◽  
Metabolic Inhibitors ◽  
Active Process ◽  
Low Concentrations ◽  
Significant Difference ◽  
Adrenalectomized Rats

In vitro studies of the flux of α-aminoisobutyrate-1-C14 (AIB) between rat thymic lymphocytes and extracellular fluid have revealed that: a) the amino acid enters cells but is not further metabolized; b) at low concentrations, similar to those of amino acids in plasma, the net influx and efflux of AIB exhibit properties of an active process; and c) influx of AIB is inhibited, and efflux stimulated, by deoxycorticosterone (DOC), by metabolic inhibitors, and by other specific steroids. In vivo studies of the distribution of AIB between serum and tissue demonstrated that administration of DOC to adrenalectomized rats inhibited concentration of AIB by thymus, diaphragm, and skeletal muscle, augmented uptake by liver, and increased the serum level of AIB. Prior adrenalectomy of donor rats resulted in no change from normal in the in vitro capacity of thymic lymphocytes to take up AIB. There was no significant difference from normal in the in vivo concentration of AIB by thymus, liver, and skeletal muscle of adrenalectomized rats, although uptake by diaphragm was decreased compared to normal control animals.

Sign in / Sign up

Export Citation Format

Share Document