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Biomedical subjects

J Knoll

Publications and source records attributed to J Knoll.

At least 127 records · Page 7Linked to original sources
PubMed1979

Effect of prostaglandin E1 and indomethacin on responses of longitudinal muscle of guinea-pig ileum to cholecystokinin.

The effect of prostaglandin E1 (PGE1) and indomethacin (IND) cholecystokinin (CCK)-induced contractions of guinea-pig isolated ileum longitudinal muscle were studied. PGE1 (2.8--28 nM) consistently and dose dependently increased the contractions evoked by CCK (indirect muscle stimulation) or by ACh. IND (2.7 microM) decreased the contractions to both compounds and this was reversed with 2.8--7 nM PGE1. Pretreatment of the preparations with phentolamine (2.6 microM) or pretreatment of the animals with reserpine (2 mg/kg i.p. 24 h before killing) did not affect PGE1 potentiation or IND inhibition of CCK-induced contractions. The results indicated that PGE1 potentiated CCK-induced contractions of the longitudinal muscle of guinea-pig ileum by increasing the response to released ACh. Experiments with IND suggested that endogenous PGs may modulate the effect of CCK or related gastrointestinal hormones.

Acetylcholine↗
PubMed1979

Azidomorphines: a new family of potent analgesics with low dependence capacity.

1. Structure-activity relationship studies with new semi-synthetic isomorphine derivatives revealed that substitution of an azido group in position 6 (azidomorphines) greatly increases the analgesic potency whereas tolerance and dependence liability tend to decrease. 2. Azidomorphine (6-deoxy-6-azidodihydroisomorphine) and 14-hydroxyazidomorphine (6-deoxy-6-azidodihydro-14-hydroxyisomorphine) being in animal tests 40-300 times more potent than morphine, are the most effective analgesics among the semi-synthetic morphine alkaloids. 3. As demonstrated on mice, rats and rhesus monkeys, a remarkable dissociation between the analgesic potency and physical dependence capacity was the result of the introduction of the 6-azido group into dihydroisomorphine. 4. A dichotomy between analgesic effect and tolerance and addiction liability was demonstrated with azidomorphine also in man and the new substance proved to exert significantly less untoward effects than either morphine or pentazocine. 5. Rymazolium (Probon) a new non-narcotic analgesic which strongly potentiates the analgesic and antagonizes the respiratory depressant effect of morphine alkaloids in animals proved to hinder the development of tolerance to morphine in animals and man. 6. The azidomorphine-rymazolium association was found to be less respiratory depressant than azidomorphine administered alone. In patients with chronic intractable pain, an association of azidomorphine (0.5 mg) and rymazolium (150 mg) achieved total pain relief without noticeable euphoria and none of the twelve patients showed, according to the Himmelsbach scoring system, acute abstinence syndromes after nalorphine administration.

Analgesics↗
PubMed1979

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido [1,2-a] pyrimidine-3-carboxamide (Chinoin-127), a potent non-narcotic analgesic and antiinflammatory agent.

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidine-3-carbamide (Chinoin 127), a non-narcotic analgesic with potent antiinflammatory activity is described. Chinoin-127 is more potent as an analgesic in the hot plate, Randall-Selitto and writhing tests than is acetylsalicylic acid (ASA) and an effective antiphlogistic agent in a battery of tests (carrageenin, kaolin and dextran induced rat paw edema, Northover test, carrageenin induced abscess, implanted cotton pellet method, adjuvant arthritis) used for measuring antiinflammatory activity. The PG-synthesis inhibitors (indometacin, suprofen) were found to be devoid of analgesic activity, and great test-dependent variations in their antiinflammatory effect were observed. They proved to be inactive in the Northover test. Unusual grade of inhibition in the carrageenin-induced rat paw edema test was obtainable by the simultaneous administration of Chinoin 127 and indometacin.

Abscess↗
PubMed1979

The effect of prostaglandin E1 on acetylcholine release from the cat brain.

Cerebral ventricular perfusion with prostaglandin E1 (PGE1, 1.4 X 10(-8) M) reduced the release of acetylcholine (ACh) into the ventriculo-cisternal perfusate of the unanaesthetized cat's brain. The samples of effluent were assayed on the isolated guinea-pig ileum. Neither a halving (1.07 X 10(-3) M) nor a threefold rise (6.45 X 10(-3) M) in the calcium concentration of the perfusate had any effect on the spontaneous release of the cholinergic transmitter. The action of PGE1 was counteracted by decreasing and potentiated by increasing the extracellular calcium concentration. Polyphloretin phosphate (PPP, 10(-4) g/ml) in itself did not significantly affect the ACh outflow. Preperfusion however, with this drug readily antagonized the depressant effect of PGE1. Ouabain (2.0 X 10(-5) M) added to the perfusion fluid increased the ACh output from the cat brain, and PGE1 prevented this effect of ouabain. A single intraventricular injection of 6-hydroxydopamine (1 mg) counteracted the inhibitory effect of PGE1 on spontaneous ACh release. A perfusion with the potent PG synthesis inhibitor suprofen (3.8 X 10(-7) M) did not influence change the mean output of the transmitter. Our data indicate that PGE1 reduces ACh release in the CNS via a pre- or postsynaptic modification of monoaminergic neurotransmission.

Acetylcholine↗
PubMed1978

Comparative effects of prostaglandin F2alpha and A2 on the cardiac transmembrane potentials.

PGF2alpha and PGA1 similarly to PGE1 and PGE2 exerted a dose-dependent dual effect on the maximum rate of depolarization (Vmax) of the cat and guinea-pig left auricle. Low concentrations (0.5 and 1.0 microgram/ml) of PGF2alpha caused a marked increase of Vmax which was proportional to the dose in both species, while the overshoot (OS) remained unchanged. PGF2alpha in a dose of 5 micrometer/ml significantly decreases OS but did not alter Vmax, in a dose of 10 microgram/ml, however, evoked a considerable decrease of Vmax, too. These changes were not related to those in the resting potential (RP). With respect to the repolarization phase no biphasic effect was observed. PGA1 in a dose of 0.02 microgram/ml significantly increased Vmax and RP, too. In the presence of 0.1 microgram/ml of PGA1 Vmax remained unchanged, only a significant hyperpolarizing effect could be observed. A higher concentration (1.0 microgram/ml) of PGA1 evoked a significant decrease of Vmax, without changing RP. The examined concentrations of PGA1 accelerated the initial repolarization (20 and 50% repolarization phase).

Animals↗
PubMed1978

Effect of verapamil and D 600 on cardiac transmembrane potentials.

The effects of verapamil and D 600 on the transmembrane potential of guinea pig and cat left auricles were analysed using KC1 filled intracellular microelectrodes. Verapamil (2 microgram/ml) seemed to have no considerable effect on resting potential (RP) and on the maximum depolarization rate (Vmax) of the electrically driven guinea pig auricle. This was the case when transmembrane potential measurements performed for an hour were averaged. If the data were evaluated in relation to time, a clear-cut biphasic effect of verapamil became obvious: in the period from 10 to 30 min after verapamil application a significant (5%) increase of RP and of Vmax (26%) could be seen; these changes became progressively slighter during the period from 30 to 50 min after verapamil application, while in the third phase (50 to 70 min) a significant decrease of both RP (11%) AND Vmax (27%) occurred in the guinea pig auricle. Similar kinetics of the verapamil effect were observed in the cat auricle. Verapamil at higher (3 microgram/ml) concentration decreased RP and Vmax. The time dependent dual effect of verapamil is probably unrelated to the inhibition of Ca conductivity as D 600, a more effective inhibitor in a corresponding dose (0.5 microgram/ml), failed to produce this type of time-dependent effect. A fourfold increase of Ca2+ concentration prevented the delayed depressing effect of 2 microgram/ml verapamil, but did not influence its early stimulating effect.

Action Potentials↗
PubMed1978

Absorption, distribution and elimination of drotaverine.

14C-drotaverine [1(3',4'-diethoxybenzale)-6, 7-diethoxy-1, 2,3, 4-tetrahydroisoquinoline. HCl; No-SpaR] is well absorbed after subcutaneous and oral administration in mice. Its distribution is not specific. After intravenous administration the drug penetrates rapidly into every organ as indicated by whole body autoradiography. In the first hours the concentration of drotaverine was higher in the intestinal wall than in the other tissues. The concentrations of drotaverine in the organs decrease soon after administration and the drug is excreted mainly with the bile as beta-glucuronide; 60% of the dose was in the bile collected during 5 hours. During 96 hours of observation, 67% of the radioactivity administered was found in the stools while only 20% of it was eliminated with urine.

Absorption↗