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Biomedical subjects

M D Hynes

Publications and source records attributed to M D Hynes.

At least 37 records · Page 2Linked to original sources
PubMed1982

Novel phenylpiperidine opioid antagonists and partial agonists: effects on fluid consumption.

The effects of five opioid antagonists, a racemate partial agonist and its agonist and antagonist optical isomers were studied on deprivation-induced drinking. All compounds had a phenylpiperidine nucleus. The antagonists produced dose-related decreases in drinking, and the potencies for decreasing drinking correlated with morphine-antagonist doses. The racemic partial agonist and its agonist isomer decreased drinking at doses higher than those which produced marked analgesia. Within the class of phenylpiperidine drugs studied, some had less specificity than naloxone for the mu-receptors as compared to the delta-receptor, but the suppression of drinking was not related to changes in mu-to-delta ratios.

Animals↗
PubMed1982

Evidence that ethanol-induced impairment of roto-rod performance is not mediated by opioid mechanisms.

1. The performance of mice, trained to remain on a roto-rod, was significantly impaired by both morphine and ethanol. The behavioral impairment was dose dependent. 2. Naloxone (10, 30 and 100 mg/kg) was found to antagonize only the morphine-induced impairment of roto-rod performance. 3. Animals made tolerant to morphine did not perform better than non-tolerant animals when challenged with ethanol, but did perform better when challenged with morphine. As such, no cross tolerance developed between ethanol and morphine in this model. 4. These results suggest that the ethanol-induced impairment of roto-rod performance is not mediated via opioid mechanisms.

Animals↗
PubMed1982

Lack of an opiate response to nitrous oxide in mice resistant to the activity-stimulating effects of morphine.

Nitrous oxide, like morphine, stimulates locomotor activity in the CD-1, C-57 and C-3H mouse strains. This stimulation of locomotor activity is antagonized by the narcotic antagonist naltrexone (3 and 30 mg/kg). There are several strains (A/J and DBA/2J) of mice in which morphine does not stimulate locomotor activity. Mice resistant to this behavioral effect of morphine show a stimulation of locomotor activity in response to nitrous oxide which is not blocked by naltrexone. These results provide new data linking the effects of morphine and nitrous oxide. The opiate-like stimulation of activity produced by nitrous oxide may result from the release of endogenous opiate-like substances. Nitrous oxide causes a displacement of [3H]naloxone from brain opiate receptors labeled in vivo in the CD-1 mouse strain. In marked contrast to these results, nitrous oxide administration to the A/J and DBA/2J morphine-resistant strains failed to displace [3H]naloxone from opiate receptors labeled in vivo. Thus, variations in the response to nitrous oxide may not only be strain-dependent but possibly related to deficits in the response of or interaction with the endogenous opiate system.

Animals↗
PubMed1982

Degree of selectivity of pergolide as an agonist at presynaptic versus postsynaptic dopamine receptors: implications for prevention or treatment of tardive dyskinesia.

Pergolide mesylate is a potent dopamine agonist that is being evaluated clinically in Parkinson disease, hyperprolactinemia, and other diseases. Pergolide activates both presynaptic and postsynaptic dopamine receptors, with some apparent selectivity for the presynaptic dopamine autoreceptors. In rats, low doses of pergolide (0.01 mg/kg or less, intraperitoneally) decreased dopamine turnover in brain, decreased serum prolactin concentration, and reduced blood pressure in spontaneously hypertensive rats. At somewhat higher doses (0.05 mg/kg or more, intraperitoneally), pergolide caused contralateral turning in nigrostriatal-lesioned rats, elevation of serum corticosterone, and hypermotility with stereotyped behavior. All of these actions are thought to be due to stimulation of dopamine receptors at various sites, but the data suggest that pergolide may have preferential affinity for presynaptic dopamine receptors. If low doses of pergolide can reduce dopaminergic transmission by activating presynaptic receptors that control dopamine release, then this action might be therapeutically useful in treating schizophrenia without causing tardive dyskinesia or in the treatment of tardive dyskinesia. The long duration of action of pergolide seen in animal and human studies could be an important advantage over some other dopamine agonists such as apomorphine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Tolerance to nitrous oxide analgesia in rats and mice.

The purpose of these experiments was to characterize the nature of tolerance to the analgesic action of nitrous oxide. Analgesia was assessed in rats using a tail-flick latency test and in mice using an abdominal constriction test. Rats and mice were exposed to nitrous oxide, 75 per cent, the balance oxygen, continuously for 16--18 hours. On re-exposure to nitrous oxide 30 min later, these animals were found tolerant to nitrous oxide in that the analgesic response was decreased by at least 50 per cent. Animals tolerant to nitrous oxide were not tolerant to morphine. Morphine (0.25--1.5 mg/kg) produced equal degrees of analgesia in control and nitrous oxide-tolerant mice and rats. In contrast, rats made tolerant to morphine by repeated daily injections of as much as 400 mg/kg subcutaneously or by subcutaneous implantation of morphine pellets (75 mg, twice) showed a decreased analgesic response to nitrous oxide. Thus the cross-tolerance between nitrous oxide and morphine appears unique in that it is unidirectional.

Anesthesia, General↗
PubMed1976

Effects of cholinergic agonists and antagonists on morphine-withdrawal syndrome.

The effects of pilocarpine, atropine and dexetimide were studied on the occurrence and intensity of morphine-withdrawal signs observed after cessation of chronic morphine injections. Pilocarpine was effective in reducing both 'wet-dog' like body shakes and aggression but it increased diarrhea and weight loss. Pretreatment with atropine blocked all of the effects of pilocarpine on withdrawal signs. Methylscopolamine pretreatment blocked only diarrhea. The administration of atropine or dexetimide produced no significant effect on any of the withdrawal signs. These results indicate a role for central cholinergic mechanism in narcotic withdrawal.

Animals↗
PubMed1975

Paradoxical absence of aggression during naloxone-precipitated morphine withdrawal.

Aggression, which is normally seen during withdrawal from narcotics, could not be produced in morphine-dependent rats by the administration of naloxone at doses which causes other signs of withdrawal. Apomorphine injected instead of naloxone was capable of producing aggression, without other withdrawal signs. Naturally occurring aggression (72-hr withdrawal) was enhanced by apomorphine and unaffected by naloxone.

Aggression↗