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Biomedical subjects

J Knoll

Publications and source records attributed to J Knoll.

At least 145 records · Page 8Linked to original sources
PubMed1977

Effect of prostaglandins E1 and F2 alpha on neuromuscular transmission in the frog sartorius muscle.

End plate potentials (e.p.p.s.) and miniature end plate potentials (m.e.p.p.s.) were recorded intracellularly at the neuromuscular junction of the frog sartorius muscle. Addition of as little as 8.5 x10(-8)M PGE1 reduced the mean m.e.p.p. frequency. The mean amplitude of m.e.p.p.s was not changed, the mean amplitude of the e.p.p.s and the quantum content of the transmitter released by a nerve impulse was slightly reduced. A decrease in mean m.e.p.p. frequency was also seen in response to the administration of 8.5 x 10(-8)M PG2 alpha. The mean amplitude of e.p.p.s and m.e.p.p.s and the quantum content remained unchanged. The possible presynaptic mode of action of PGs in the preparation of discussed.

Animals↗
PubMed1977

The pharmacology of N-substituted azidomorphines.

N-allylnorazidomorphine (NAM), N-allyl-14-hydroxynorazidomorphine (NOAM), N-cyclopropylmethylnorazidomorphine (CAM) and N-cyclopropylmethyl-14-hydroxynorazidomorphine (COAM) were synthetized and their pharmacological effect in comparison to naloxone and naltrexone were analyzed. While naloxone and naltrexone are pure antagonists at all points, the N-substituted norazidomorphines were found to be more potent antagonists than naloxone in some of the tests and extremely potent pure agonists in others. Using CAM for routine work we differentiated between opiate A-receptors which are stimulated and opiate B-receptors which are antagonized by CAM. Opiate A-receptors were found to be involved in the behavioral disturbances (inhibition of conditioned avoidance responses, characteristic EEG changes, elimination of slow wave and paradoxical sleep, etc.) caused by the opiates. The guinea-pig ileum and mouse vas deferens are the suitable isolated organs for testing A-receptors. Opiate B-receptors are responsible for the analgesic, antitussive, cataleptic, respiratory depressant and hypotensive effects of the opiates. The isolated nictitating membrane of the cat is an appropriate model for testing the B-receptors. The hypothesis is proposed that A-receptors relate to cholinergic and B-receptors to adrenergic mechanisms; the N-substituted norazidomorphines are tools for the analysis of the two kinds of opiate receptors.

Acetylcholine↗
PubMed1977

Azidomorphines and homopyrimidazols: a new approach to the ideal analgetic.

Azidomorphines, new semi-synthetic isomorphine alkaloids and homopyrimidazols (1, 5-diazanaphtalenes), two new families of compounds favourably enlarging the scope of analgetics, were developed. Azidomorphine, a 40--50 times more potent analgetic in man than morphine, showed a remarkably great dissociation between analgetic potency and dependence capacity and proved to exert significantly less unfavourable effects than either morphine or pentazocine. Probon (Rymazolium), the first compound of the homopyrimidazol series, introduced to therapy as a new minor analgetic, potentiated the analgetic and antagonized the respiratory depressant effect of morphine and its derivatives. In patients with chronic intractable pain, a combination of azidomorphine (0.5 mg) and Probon (150 mg) achieved total pain relief without noticeable euphoria and none of the patients subjected to nalorphine-precipitation showed signs of abstinence according to the Himmelsbach scoring system. Since both the azidomorphines and the homopyrimidazols are unexploited new families, further progress in detail structure-activity relationship studies seems quite promising.

Analgesics↗
PubMed1976

Neuronal peptide (enkephalin) receptors in the ear artery of the rabbit.

Methionine-enkephalin methylester (MEM) and leucine-enkephalin (LE) inhabit the vasoconstrictor responses of the rabbit ear artery to nerve stimulation by acting on a specific neuronal peptide (enkephalin)-receptor insensitive to opiate agonists. The tetrapeptide: H-Tyr-Gly-Phe-Leu-OCH3 is ineffective. This is the first instance of enkephalins acting in an organ devoid of receptors. In a new test for the analysis of opiate receptors, MEM (ID50=6.9 X 10(-9) M) was a potent inhibitor of transmission. The presence was shown of opiate receptors in the brain which were insensitive to high i.v. or intraventricular doses of enkephalins. It is concluded that enkephalins are not natural ligands to the opiate receptors, but that some of the receptors confuse these structures because of similar characteristics which determine the binding of both opiates and peptides.

Animals↗
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↗
PubMed1976

Inhibitory effects of prostaglandin E1 on responses of rabbit ear artery to nerve stimulation and on release of norepinephrine.

PGE1 in concentrations of 7 x 10(-9) to 4.5 x 10(-7) M inhibited the vasoconstrictor responses of the perfused rabbit ear artery to nerve stimulation. The degree of inhibition was dependent on the concentration of PGE1, as well as on the train length and frequency of stimulation. The vasoconstriction produced by norepinephrine was not altered by 1.1 x 10(-7) M PGE1. This substance markedly reduced the stimulation-evoked outflow of 3H-norepinephrine from the artery. The findings indicate that PGE1 inhibits the vasoconstrictor responses of rabbit ear artery to sympathetic nerve stimulation by reducing the release of the sympathetic transmitter for adrenergic nerve endings.

Animals↗
PubMed1976

Inhibition of neuromuscular transmission by prostaglandin E1 in the circular muscle of the guinea-pig vas deferens.

Pressure increases elicited by contractions of the circular muscle of the isolated guinea-pig vas deferens in response to nerve stimulation were recorded. In contrast to longitudinal muscle which contracted in response to 1--50 pulses, circular muscle responded only to longer trains of pulses (10--500) at a frequency of 10 Hz. Atropine (1.4 muM) caused a slight depression of responses to 100 shocks. Phentolamine at a concentration of 2.6 muM failed to inhibit the response to stimulation, but a higher concentration (53 muM) caused a definite blockade. Guanethidine (25 muM) strongly reduced the responses. With a stimulus train of 100 pulses no inhibition by prostaglandin E1 (PGE1) (0.028 muM) could be demonstrated; however, at a lower number of shocks (20--50) a clearcut depression was observed. The lower the number of pulses the more marked was the depression. The observation that PGE1 failed to block the contractions evoked by noradrenaline (59 muM) suggests a presynaptic inhibitory action of the prostaglandin. It is suggested that noradrenaline is the transmitter in both muscle coats of the guinea-pig vas deferens and that the neuroeffector junctions are sensitive to the effect of PGE1.

Animals↗