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Biomedical subjects

K Jhamandas

Publications and source records attributed to K Jhamandas.

121 records · Page 7Linked to original sources
PubMed1977

Muscarinic feedback inhibition of acetylcholine release from the myenteric plexus in the quinea pig ileum and its status after chronic exposure to morphine.

Atropine (10(-8)-10(-6) M) produced a dose-related increase in the release of ACh from the electrically stimulated longitudinal muscle-myenteric plexus preparation. This increase in release was frequency dependent, being greater at low frequencies of stimulation where the pulse release of ACh was greater than at high frequencies. The muscarinic agonist oxotremorine (up to 100 micrometer) did not inhibit ACh release although 100 micrometer oxotremorine did antagonize the ability of atropine to increase release. The effect of chronic exposure to morphine, both in vivo and in vitro, on the reactivity of muscarinic receptors mediating this increase was examined. Neither the control rate of ACh release nor the dose-response curve for atropine were altered by (a) an 8-day morphine injection schedule, and (b) exposure of the tissue to morphine in the bath for 90 min. The results of this study support the existence of a muscarinic feedback mechanism which controls ACh release from the myenteric plexus. Chronic exposure to morphine does not produce specific changes in the muscarinic receptor mediating this inhibition.

Acetylcholine↗
PubMed1976

Effects of acute and chronic methadone treatment of the uptake of 3H-5-hydroxytryptamine in rat hypothalamus slices.

Effects of in vitro methadone and several other narcotics were investigated on 3H-5-HT uptake in rat hypothalamus slices. The results indicated that d, l-methadone and levorphanol had slightly greater inhibitory action on the uptake than the isomers, d-methadone and dextrorphan, respectively. Morphine, diacetylmorphine and the narcotic antagonist naloxone produced a considerably weaker inhibitory effect. After an acute injection of methadone, but not morphine, the uptake of 5-HT by hypothalamic slices of treated animals was inhibited. The chronic treatment of rats with methadone for 18 days had no significant effect on the uptake, but following the withdrawal of this treatment for 2 weeks the 5-HT uptake was significantly elevated. The inhibitory effects of in vitro methadone in the hypothalamus slices were not modified by the chronic drug treatment.

Animals↗
PubMed1976

Morphine-naloxone interaction in the central cholinergic system: the influence of subcortical lesioning and electrical stimulation.

1 The opiate antagonist naloxone, injected or topically applied to the cerebral cortex, had no significant effect on the spontaneous output of cortical acetylcholine (ACh) in rats. 2 Morphine (2.5 mg/kg) administered intravenously inhibited the release of cortical ACh. A subsequent injection of naloxone rapidly reversed morphine-induced inhibition, and produced a sustained increase in the release of ACh. Topical application of naloxone solutions, after morphine, produced a slow and weak reversal of its inhibitory action. 3 Destruction of the medial thalamus abolished both the inhibitory effects of morphine on the cortical ACh release, and its antagonism by naloxone administered after the agonist. 4 Injection of naloxone in a low dose (0.1 mg/kg) increased the release of cortical ACh provoked by electrical stimulation of either the medial thalamus or the reticular formation in normal rats. In the morphine-dependent rat, naloxone also facilitated the evoked release and its action was greater than in control animals. The facilitatory effect of naloxone on the cortical release evoked by stimulation of the medial thalamus was greater than its effect on the release evoked by stimulation of the reticular formation in both normal and morphine-dependent rats. 5 Naltrexone, a narcotic antagonist, also facilitated the electrically stimulated release of cortical ACh. 6 It is suggested that (a) morphine and naloxone act at a subcortical site, probably the medial thalamus, to modify the cortical ACh release and that (b) naloxone may facilitate the electrically-induced release of ACh in the CNS by antagonizing the effect of the endogenous morphine-like factor, enkephalin.

Acetylcholine↗
PubMed1975

Comparative effects of opiate agonists methadone, levorphanol, and their isomers on the release of cortical ACh in vivo and in vitro.

The effect of analgesically active opiate agonists dl-methadone, levorphanol, and their less active forms d-methadone and dextrorphan, respectively, were tested on, (a) the spontaneous release of cortical acetylcholine (ACh) in vivo; (b) the spontaneous and K+-evoked release of cortical ACh in vitro. The injections of dl-methadone, but not d-methadone, inhibited the output of ACh in vivo. Naloxone completely reversed this effect of methadone. Levorphanol in small doses inhibited, and in larger doses stimulated, the in vivo release of ACh. Both effects were antagonized by naloxone. Its dextroisomer dextrorphan was completely inactive. The in vitro release of ACh from cortical slices was inhibited by all four agents. The effects of analgesically active opiates dl-methadone and levorphanol on the in vitro release were not clearly separable from the effects of their inactive forms d-methadone and dextrorphan.

Acetylcholine↗
PubMed1974

Modification of brain acetylcholine release by morphine and its antagonists in normal and morphine-dependent rats.

1 The spontaneous release of acetylcholine (ACh) from the cerebral cortex of control and morphine-dependent rats was investigated. The rate of resting output of ACh in morphine-dependent animals was lower than that in the control animals.2 Administration of naloxone and nalorphine to morphine-dependent rats was followed by a significant rise in the release of cortical ACh. In control rats no such increase in the release of ACh occurred after similar injections of narcotic antagonists.3 Injections of morphine produced a consistent decrease in the rate of spontaneous release of cortical ACh in the control rats, but similar injections in the dependent rats did not produce a decrease in the rate of cortical ACh release.4 The relevance of these results with regard to development of the narcotic abstinence syndrome is discussed.

Acetylcholine↗
PubMed1971

Effects of narcotic analgesics and antagonists on the in vivo release of acetylcholine from the cerebral cortex of the cat.

1. In cats under light allobarbitone anaesthesia, the effects of intravenous injections of narcotic and non-narcotic analgesics, of a general depressant, and of narcotic antagonists were investigated on the spontaneous release of acetylcholine (ACh) from the surface of the sensorimotor cortex.2. The narcotic analgesics morphine (0.1, 1.0 and 5 mg/kg), meperidine (1.0 and 2.0 mg/kg), methadone (1.0 mg/kg) and codeine (5.0 and 10.0 mg/kg) greatly reduced ACh release.3. The non-narcotic analgesics pentazocine (1.0 and 2.0 mg/kg) and propoxyphene (5.0 and 10.0 mg/kg) as well as the depressant chlorpromazine (0.25, 0.5 and 1.0 mg/kg) also greatly reduced ACh release.4. Two of the three narcotic antagonists examined, levallorphan (0.1, 1.0 and 5 mg/kg) and nalorphine (1.0 mg/kg) had the property of reducing ACh release. They were thus partial agonists. With levallorphan the greatest reduction occurred with the smallest dose injected and the effect was regularly obtained, whereas with nalorphine a reduction was obtained in some experiments only. The third, naloxone, was a specific narcotic antagonist and did not reduce the ACh release in any dose (0.01, 0.1, 0.5 and 1.0 mg/kg) examined. In a dose of 1.0 mg/kg it actually produced a small increase in Ach release.5. Naloxone (0.1-1.0 mg/kg) restored the reduction in ACh release produced by the narcotic analgesics and by the partial agonist levallorphan. It partially restored the reduction produced by the non-narcotic analgesics and by nalorphine, but had no effect on the reduction produced by chlorpromazine.6. The relevance of these results with regard to analgesia and to the narcotic abstinence syndrome is discussed.

Acetylcholine↗
PubMed1970

Effects of drugs acting alone and in combination on the motor activity of intact mice.

1. When administered to intact white mice, the central depressants-diphenhydramine, promethazine, chlorpromazine, gammahydroxybutyrate, gammabutyrolactone, hyoscine, and pethidine-produced sedation in small doses, but excitement and convulsions in higher doses. When given to mice pretreated with subanaesthetic doses of phenobarbitone these drugs abolished the righting reflex both in convulsant doses (hyoscine excepted) and in non-convulsant doses. These effects are similar to the effects previously observed with local anaesthetics.2. Meprobamate, diazepam and chlorpromazine produced a loss of righting reflex both when given alone and following phenobarbitone. When given alone in higher doses, chlorpromazine induced convulsions.3. The central stimulants bemegride and picrotoxin antagonized the loss of righting reflex produced by phenobarbitone, but nikethamide, caffeine and strychnine did not alter the depressant effects of phenobarbitone.4. On the basis of these and previous studies with intact white mice a tentative classification of drugs having generalized depressant and stimulant effects on the central nervous system was proposed and discussed.

Adjuvants, Anesthesia↗
PubMed1970

Effects of general depressant drugs on the electrical responses of isolated slabs of cat's cerebral cortex.

1. In the neuronally isolated cortex of the cat, local application of diphenhydramine, promethazine, gammahydroxybutyrate, gammabutyrolactone, gamma aminobutyric acid, hyoscine and pethidine, and the intravenous injection of diazepam and meprobamate depressed or abolished the surface negative and surface positive response to direct stimulation and raised the stimulus threshold of the positive burst response. These effects were the same as previously demonstrated for general and local anaesthetics on the same preparation.2. Chlorpromazine produced a similar depression in small concentrations but caused spontaneous activity in higher concentrations.3. In contrast to local application, pethidine when given by intravenous injection in a high dose produced convulsant activity in the isolated cortical slab. The possibility was suggested that the convulsant activity was produced by a metabolite of pethidine.4. The results of this investigation suggest that the central depression produced by a number of structurally unrelated drugs is indicative of an anaesthetic-like property of these drugs.

Action Potentials↗
PubMed1970

Effects of general stimulant drugs on the electrical responses of isolated slabs of cat's cerebral cortex.

1. In the neuronally isolated cortex of the cat, local application of bemegride, picrotoxin, nikethamide, caffeine and strychnine facilitated the surface positive response of the isolated cortex and lowered the stimulus threshold for this response. Excepting nikethamide, they all produced convulsive discharge in the isolated cortex unrelated to the applied stimulus.2. Local application of glutamate to the cortex produced spreading depression, which was sometimes preceded by spontaneous positive bursting.3. In contrast to the "general depressants" which produce a relatively consistent pattern of effects on the electrical responses of isolated cortex, the "general stimulants", although they all have excitatory effects on isolated cortex, each produced a greatly different type of electrical response in the isolated cortex, suggesting that several different mechanisms of action are responsible for their effects.

Action Potentials↗