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Biomedical subjects

F F Foldes

Publications and source records attributed to F F Foldes.

At least 55 records · Page 3Linked to original sources
PubMed1982

[Neuromuscular and cardiovascular effects of Duador, a new short-acting nondepolarizing muscle relaxant].

The neuromuscular blocking and circulatory effects of a recently synthesized relatively short acting nondepolarizing muscle relaxant, Duador, have been investigated in anaesthetized patients. Duador appears to be a potent muscle relaxant with intermediate duration of action. It had no cumulative effects even after as many as five maintenance doses. Doses of 0.4 mg/kg provided ideal intubating conditions in 2 min, though maximal blockade only developed in about 6 min. Duador was easily antagonized by edrophonium and no signs of recurarisation have been observed. The initial dose of Duador caused a mean 28% increase in heart rate. The increase in heart rate was inversely proportional to the control rate. Repeat doses did not cause further elevation in frequency. Duador had no effect on mean blood pressure.

Adult↗
PubMed1981

The influence of stimulation parameters on the potency and reversibility of neuromuscular blocking agents.

Voluntary muscle movements in mammalian muscles are initiated by short trains of 16 to 60 Hz impulses (Zierler, 1974). Despite this in most neurophysiological and neuropharmacological studies either single stimuli of 0.1 to 2 Hz or 5 to 10 sec 50 to 500 Hz tetani have been employed. Neither of these two types of stimuli are ideal for the testing of the functional integrity of the motor unit. Stimulation with single impulses, at slow rates, does not reveal incipient pathological or drug induced defects. Recovery of neuromuscular (NM) activity after 5 to 10 sec tetanic stimulation is prolonged and after repeated stimulation of this type the preparations decay rapidly. Stimulation of 0.1 sec trains of 50 Hz impulses applied every 10 to 20 sec eliminate the above disadvantages. This type of stimulation represents adequate challenge for revealing more moderate degrees of functional defects of the myoneural apparatus without causing rapid decay of the in vitro or in vivo preparations. In agreement with this the ED50 of NM blocking agents were found to be significantly lower in both the in vitro phrenic nerve-hemidiaphragm preparation and the in vivo sciatic nervetibialis anterior muscle preparation of rats during stimulation with 0.1 sec trains of 50 Hz impulses, than when single stimuli of 0.1 Hz were used. Recovery of the in vitro preparations after washout or in vivo after discontinuation of the infusion was also slower during stimulation with short trains of tetani. The antagonist potency of anticholinesterases or 4-aminopyridine and maximal recovery after the use of the optimal concentrations of these antagonists was less in the preparations stimulated with short trains of tetani than in those stimulated with single impulses.

Acetylcholine↗
PubMed1980

Pharmacology of ORG NC 45 compared with other non-depolarizing neuromuscular blocking drugs.

From results of pharmacological tests on the neuromuscular and autonomic blocking actions of a series of pancuronium analogues, Org NC 45, the C16 monoquaternary analogue of pancuronium, was selected for detailed study. Org NC 45 has a non-depolarizing mechanism of action, is more rapid in onset and shorter in duration of action than pancuronium. It shows less cumulation than pancuronium or tubocurarine, and is easily antagonized by anticholinesterases and aminopyridines. Org NC 45 exhibits a low propensity to release histamine. Its ability to inhibit cholinesterases is not likely to be important at neuromuscular blocking doses. Org NC 45 possesses negligible ganglion-blocking activity and there is a wide margin between neuromuscular and vagal blocking doses. Thus cardiovascular side-effects are unlikely to occur with the use of Org NC 45. It will hydrolyse mainly to its 3-hydroxy analogue which, like Org NC 45, possesses a wide margin between neuromuscular and vagal blocking doses. Org NC 45 has a high selectivity for the neuromuscular junction and represents a potentially useful addition to the armamentarium of clinically useful muscle relaxants.

Aminopyridines↗
PubMed1980

Quantitative determination of germines. The rate of transformation of germine-3,16-diacetate in buffered solutions of pH 7.4.

Germine (GER), germine-3-monoacetate (GMA) and germine-3,16-diacetate (GDA) when treated with 9:1 mixture of concentrated sulfuric acid and glacial acetic acid yield a deep purple color with characteristic ultraviolet absorption spectra. Combination of the color reaction with TLC makes possible the quantitative determination of these compounds in buffered solutions of pH 7.4 with a > 90% yield and satisfactory accuracy. It was observed that GDA incubated in such solutions is slowly transformed into GMA. The transformation of GDA to GMA was significantly faster with higher than with lower concentrations of GDA. There was no detectable breakdown of GMA under the same experimental conditions.

Animals↗
PubMed1980

Neuromuscular drug interactions of clinical importance.

The addition of marginally effective concentrations of d-tubocurarine (d-Tc), neomycin, or polymyxin B to the organ bath of rat phrenic nerve-hemidiaphragm preparations significantly (p < 0.05 to 0.001) increased the neuromuscular (NM) blocking effect of lidocaine. When both d-Tc and neomycin or polymyxin B were added the increase of the NM effect of lidocaine was even greater (p < 0.001). Washout re-established NM transmission. The NM block produced by combinations of d-Tc, neomycin, or polymyxin and lidocaine could be reversed partially by Ca2+ or neostigmine, and completely by 4-aminopyridine. The block caused by d-Tc and lidocaine was partially antagonized by neostigmine or 4-aminopyridine., The neomycin-lidocaine or the polymyxin B-lidocaine block, however, was not antagonized by thse compounds. The concentrations of d-Tc, antibiotics, and lidocaine that caused significant block in this in vitro preparation may be present at the NM junction of patients, who in the perioperative period had received combinations of therapeutic doses of d-Tc, neomycin, other aminoglycosides, or polymyxin B and lidocaine. This may cause impairment of spontaneous respiration requiring assisted ventilation.

Animals↗
PubMed1978

The influence of temperature on neuromuscular performance.

The influence of lowering the temperature, by 10 degrees C increments, from 37 decrees C to 17 degrees C on the twitch )Pt) and tetanic (Po) tension during direct and indirect stimulation, on presynaptic acetylcholine (ACh) release and on muscle acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were investigated in vitro on the rat's phrenic-nerve-hemidiaphragm preparation. Decreasing the temperature from 37 degrees C to 17 decrees C caused a progressive increase of the isometric Pt to 195.8 +/- 9.6 (S.E. of mean) and 169.6 +/- 2.9% of control with direct and indirect stimulation respectively. This change in temperature also increased twitch duration and time to peak Pt by factors of about 4 and 6 respectively with both direct and indirect stimulation. The Po/Pt ratio did not change significantly between 37 degrees C and 27 degrees C, but dropped sharply between 27 degrees C and 17 degrees C. With direct stimulation tetanus was only maintained in 50% of the experiments at 37 degrees C and in none at 27 degrees C or 17 degrees C. With indirect stimulation tetanus was maintained in all experiments at 37 degrees C and 27 degress C and in none at 17 degrees C. Post-tetanic facilitation was greater with indirect than direct stimulation and at higher than at lower temperatures. Post-tetanic exhaustion, with both direct and indirect stimulation, was only observed at 37 degrees C. Presynaptic ACh release (pmol . g-1 . min-1) at rest and with stimulation rates of 0.1 to 50 Hz decreased by more than 60% as temperature was lowered from 37 degrees C to 17 degrees C. Cooling from 37 degrees C to 17 degrees C caused a similar decrease in the volley output (pmol . g-1 . volley-1) of ACh. Muscle-AChE and BuChE activities decreased by 34 and 52% respectively when the temperature was lowered from 37 degrees C to 17 degrees C. The findings presented indicate that the site of the facilitating effect of cooling on Pt is the muscle fiber. The facilitation is caused by the delay of the relaxation of the contracted muscle, causing prolongation of the active state and increased tension development. The decreased speed of nerve conduction and ACh release caused by cooling adversely affects neuromuscular transmission. This, however, is partially counteracted by decreased muscle-ChE activity and increased sensitivity of the postjunctional membrane to ACh caused by cooling.

Acetylcholine↗
PubMed1977

The effect of 4-aminopyridine on acetylcholine release.

The effect of 2-, and 4-aminopyridine (4-APYR) on the release mechanism of acetylcholine (ACh) from the nerve terminals of the Auerbach plexus-longitudinal muscle preparation of the guinea-pig ileum, suspended in eserinized Krebs' solution, was investigated. 2- and 4-APYR increased the release of ACh from the nerve terminals at rest and at both low and high frequency stimulation. The enhanced ACh release was found to be due to increased volley output. At lower frequency of stimulation, potentiation of ACh release was much higher than at higher rate of stimulation. 4-APYR was able to increase ACh release in the absence of [Ca2+]o. However, when a Ca-chelating agent, EDTA, was also added to the Ca-free Krebs' solution, 4-APYR was entirely ineffective. The depression of ACh release induced by Mg-excess was completely antagonized by 4-APYR. Tetrodotoxin (TTX) prevented augmentation of ACh release by 4-APYR. It is suggested that 4-APYR lowers the demand of nerve terminals for [Ca2+]o required for the excitation-secretion coupling process. The presence of a low concentration [Ca2+]o, however, is essential for the action of 4-APYR.

Acetylcholine↗
PubMed1977

The agonist and antagonist properties of N-allylenkephalins.

The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists.

Allyl Compounds↗
PubMed1977

Orientation of the oxygen atom at C-6 as a determinant of agonistic activity in the oxymorphone series.

The kinetics of various oxymorphones, their 6-methylene analogs and the 6-hydroxy-epimers corresponding to naloxone and naltrexone have been studied in the longitudinal muscle strip of the guinea-pig ileum. Substitution of the oxygen at C-6 by amethylene group slightly increased antagonistic activity of the resulting structures, without significantly influencing agonistic activity relative to the parent compound. The alpha-orientation of the hydroxy group at C-6 enhanced the agonistic property of both naloxone and naltrexone. The beta-compounds, however, were pure antagonists, with potencies similar to those of the parent keto structures.

Animals↗
PubMed1976

Clinical pharmacological studies with 6-azidomorphine.

The intravenous (i.v.) administration of 4 mug/kg 6-deoxy-6-dihydroazido-isomorphine (6-AM) base to healthy, young adult male volunteers caused no circulatory and relatively little, short-lasting respiratory depression. Of the ten volunteers all felt lightheaded, two became euphoric and when they became ambulatory at the end of the experiment, three vomited and two other became nauseated. The intramuscular (i.m.) administration of the same dose of 6-AM had considerable analgesic effect against various types of experimental pain. It was more effective against ischemic pain, than against pain induced by electrical stimulation of the earlobe or the tooth pulp and it effected severe pain more than mild or moderate pain. In the six subjects investigated, 6-AM produced significant myosis. Of the 16 subjects who received 4 mug/kg 6-AM i.m. five experienced mild euphoria, two felt lightheaded, six became pale and sweaty in the course of the experiments carried out in the sitting position. When they becam ambulatory after the completion of the experiments, two subjects vomited and six others became nauseated. The findings of this study indicate that 6-AM causes less circulatory and respiratory depression than is to be expected from equianalgetic doses of morphine. Its other side effects (e.g., nausea, vomiting) are also less frequent and severe than those encountered after the administration of comparable doses of morphine to ambulating volunteers.

Adult↗
PubMed1976

The structure-action relationship and kinetics of some naloxone and naltrexone derivatives.

The isolated longitudinal muscle preparation (with attached Auerbach plexus) of the guinea pig ileum was used to investigate the structure activity relationship and kinetics of some naloxone and naltrexone derivatives and that of cyclazocine. The agonist used for the investigation of the antagonistic effect of these compounds was 6-azidomorphine (AM). AM was found to be an about 20 times more potent agonist than morphine. In contrast to cyclazocine, which also was found to be approximately 15 times more potent agonist than morphine, naloxone had no demonstrable agonistic activity and naltrexone and the various naloxone and naltrexone derivatives had only insignificant agonistic activity with ED50/Ke ratios ranging from 2,000 to about 120,000. All compounds tested were competitive reversible antagonists of AM. 6-Methylene substitution caused an approximate 50 and 100% increase of the antagonistic activity of naloxone and naltrexone, respectively, and decreased the duration of action of naloxone. 3-Acetate or 3-nicotinate substitution decreased potency and had no effect on the duration of naloxone action. There is a correlation between tachyphylaxis observed on the inhibition of longitudinal muscle contraction and antagonist activity of narcotic agonists.

Animals↗