Biomedical subjects

D Malec

Publications and source records attributed to D Malec.

49 records · Page 3Linked to original sources

PubMedDate not supplied

The influence of histamine receptor antagonists on antinociceptive action of narcotic analgesics.

The influence of some antagonists of histamine receptors on morphine-, fentanyl-, and pentazocine-induced analgesia was studied in rats and mice. H1-receptor antagonists (benzhydramine mepyramine) potentiated analgesic action of morphine and fentanyl. Given alone in high doses they also induced a naloxone non-reversible analgesia. Analgesic effects of pentazocine were not changed by benzhydramine and mepyramine. H2-receptor antagonist-cimetidine enhanced also analgesia induced by morphine and fentanyl in rats, but it either increased (after icv injection of 50 micrograms) or decreased (after icv injection of 100 micrograms) the action of pentazocine. Thus, H1 and H2 antagonists potentiate the antinociceptive effects of morphine and fentanyl but the action of pentazocine is not changed by H1 antagonists and is affected in an inconsistent manner by a H2 antagonist cimetidine. It seems that the potentiating effect of H-antagonists is related to the opioid mu receptors.

Analgesics, Opioid↗

PubMedDate not supplied

The effect of methylxanthines on morphine analgesia in mice and rats.

The influence of various doses of caffeine and theophylline on analgesic effect of morphine was tested in mice and rats in the hot plate and tail immersion tests. Caffeine in rats potentiated the morphine analgesia in both tests in a dose-dependent manner. In mice the caffeine-morphine interaction was biphasic: lower caffeine doses (10 and 25 mg/kg) inhibited, while higher (75 and 100 mg/kg) potentiated the analgesic effects of morphine. Theophylline interacted with morphine in a manner similar to that of caffeine.

Animals↗

PubMedDate not supplied

The influence of gabaergic system on cataleptogenic action of analgesics and haloperidol.

The effect of agonists and antagonists of the gabaergic system on catalepsy induced by morphine, fentanyl and haloperidol was investigated in the rat. The compounds inhibiting gabaergic neurotransmission, bicuculline and picrotoxin, given in subconvulsive doses (0.1-0.5 mg/kg) in general do not evidently affect cataleptogenic effects of the analgesics and haloperidol. Of the gabaergic agonists muscimol (0.2-0.5 mg/kg) potentiates only the haloperidol catalepsy, without changing the action of analgesics. Aminooxyacetic acid (AOAA, 25 mg/kg) markedly potentiated the catalepsy brought about by analgesics, while weakly and insignificantly facilitated that induced by haloperidol. Baclofen in a low dose (1 mg/kg) antagonized the action of haloperidol and fentanyl, whereas in higher doses (2-8 mg/kg) it did not visibly affect the action of any investigated drugs. Thus the action of gabaergic agonists and antagonists on the analgesic and haloperidol catalepsy varies, depending on the dose and kind of the agent affecting the gabaergic system.

Aminooxyacetic Acid↗

PubMedDate not supplied

Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats.

The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.

Analgesics, Opioid↗

PubMedDate not supplied

The development of cross tolerance between ethanol and morphine.

The development of tolerance to ethanol-induced analgesia and cross tolerance between ethanol and morphine was studied in mice and rats. Chronic administration of ethanol resulted in the tolerance to its analgesic effects in rats (2.8 and 3.0 g/kg) as well as in mice (2.8 and 4.0 g/kg). Implantation of morphine pellets caused the development of cross tolerance to analgesic effect of 3.0 g/kg of ethanol in rats and 2.8 g/kg of ethanol in mice. The tolerance developed to antinociceptive effects of morphine (10 mg/kg) in chronic alcoholized mice but not in chronic alcoholized rats. These results seem to support the hypothesis on the opiate-like mechanism of ethanol action.

Analgesia↗

PubMedDate not supplied

Central action of narcotic analgesics. I. Catalepsy and stereotypy in rats and narcotic analgesics.

The action of four analgesics, belonging to various pharmacological groups (morphine, codeine, fentanyl, pentazocine), was investigated in rats in tests for catalepsy and stereotypy, the tests depending on dopaminergic brain mechanisms. Interactions of the analgesics with a number of compounds known to affect dopaminergic brain functions in tests of catalepsy and stereotypy were also studied. In some experiments nalorphine, an antagonist of narcotic analgesics, was used. Morphine, codeine and fentanyl produced catalepsy, while pentazocine, at doses up to 60 microgram/kg, did not produce this effect. Reserpine, 2 mg/kg 3 hr before drugs, potentiated catalepsy produced by analgesics, while haloperidol, 0.2 mg/kg, 2 hr earlier, did not influence morphine and codeine catalepsy, but moderately potentiated fentanyl-induced catalepsy. alpha-methyl-p-tyrosine potentiated the cataleptogenic action of fentanyl and codeine, and also, less markedly, the action morphine. D-amphetamine (2.5-10 mg/kg) and apomorphine (5 mg/kg) moderately antagonized the catalepsy induced by analgesics, while atropine did not affect it. Nalorphine, 5 mg/kg, effectively abolished the catalepsy produced by narcotic analgesics, but did not affect that produced by neuroleptics. Morphine, codeine and fentanyl slightly inhibited apomorphine stereotypy, and evidently antagonized stereotypy produced by amphetamine. Pentazocine did not affect or slightly potentiated the both types of stereotypy. It is concluded that morphine, codeine and fentanyl, in contrast to pentazocine, inhibit behavioral activities depending on central dopaminergic functions in the rat. The mechanism of this action is most probably indirect, and seems to be related to the dopaminergic presynaptic functions.

Animals↗

PubMedDate not supplied

Central action of narcotic analgesics. VI. Further studies on the participation of serotonin in the action of analgesics.

The effects of agents changing the cerebral serotonin (5-HT) level on the action of morphine, codeine, fentanyl and pentazocine were tested in rats with the tests of catalepsy and analgesia (hot plate). In addition, the effect of analgesics of the level and turnover of cerebral 5-HT was studied. Depression of the cerebral level of 5-HT usually antagonized the behavioral effects of analgesics, but the effect varied with the agent depressing the 5-HT level. The serotonergic influences in catalepsy seem to be more pronounced than in analgesia. An increase in the cerebral level of 5-HT may potentiate the analgesic and prolonged the cataleptogenic effects of some drugs (morphine and pentazocine), not affecting the effect of others (fentanyl, codeine). The potentiation by morphine of the turnover of cerebral 5-HT in rats is not a common property of analgesics agents.

5-Hydroxytryptophan↗

PubMedDate not supplied

The influence of naloxone on the effects of adenosine receptor agonists in analgesic tests and binding studies.

Naloxone (1 mg/kg ip) reduced analgesic effect of R-phenylisopropyladenosine (R-PIA-0.2 mg/kg sc) in hot plate and tail-immersion tests in mice and in tail-immersion test in rats. Also the effect of 2-chloroadenosine (2-CADO-2 mg/kg sc) was significantly reduced by naloxone in mice in both nociceptive tests. Naloxone induced partial reduction of analgesic effects of 5'-N-ethylcarboxamideadenosine (NECA-0.02-0.05 mg/kg sc) in mice and rats. Binding studies revealed that the affinity of adenosine agonists (R-PIA and NECA) to opioid receptors was about 5000 times weaker than the corresponding affinity of naloxone.

2-Chloroadenosine↗

PubMedDate not supplied

Agonists and antagonists of adenosine receptors and morphine withdrawal syndrome in rats.

The compounds activating adenosine system alleviated morphine withdrawal syndrome (the number of escape attempts and body shakes) in rats. Body shakes were decreased mostly by N-ethylcarboxamidoadenosine, cyclohexyladenosine, dipyridamole and 2-chloroadenosine, while R-phenylisopropyladenosine very strongly decreased the number of escape attempts. Adenosine receptor antagonists (caffeine and theophylline) increased the number of escape attempts in morphine-dependent rats. Caffeine (10 mg/kg), administered preventively, antagonized the inhibitory effects of adenosine analogs. These results suggest the existence of relation between opioid receptors and the adenosine system.

Adenosine↗

PubMedDate not supplied

The influence of new 9-(omega-[4-(2-pyrimidinyl)-1-piperazinyl]alkyl) pyrimidino[2,1-f]purines on the central nervous system.

Synthesis and the results of preliminary pharmacological evaluation of four new 9-substituted pyrimidino[2,1-f]purines, containing pyrimidinyl-piperazine substituent are described. Some of these substances induced hypothermia, antagonism of amphetamine action and neurotoxic effects. All compounds had weaker activity on the central nervous system than previously studied compounds containing phenyl-piperazine substituent.

Animals↗

PubMedDate not supplied

Purinergic receptors.

The aim of the present paper was characterization of purinergic receptors specific for nucleotides (P2) and nucleosides (P1). Their subclassification, distribution and functions have been briefly described.

Animals↗

PubMedDate not supplied

Influence of adenosinergic drugs on ethanol withdrawal syndrome in rats.

The influence of adenosine, its analogs: (-)N6-(R-phenylisopropyl)-adenosine (R-PIA), N6-cyclohexyladenosine (CHA), 5-(N-ethylcarboxamido)-adenosine (NECA), adenosine uptake inhibitor-dipyridamole, and theophylline and caffeine (adenosine receptor antagonists) on ethanol withdrawal syndrome was investigated in rats. Adenosine (100 mg/kg ip), all adenosine analogs and dipyridamole (30 mg/kg ip) reduced the number of rats in which audiogenic convulsions appeared. Caffeine and theophylline (5-25 mg/kg ip) did not influence significantly the audiogenic seizures, but they antagonized the depressing effects of adenosine analogs on these withdrawal symptoms. The results suggest that adenosine mechanisms in the brain may be implicated in the development of ethanol withdrawal syndrome.

Adenosine↗

PubMedDate not supplied

Haloperidol-induced catalepsy is influenced by adenosine receptor antagonists.

Cataleptogenic effects of haloperidol (1 mg/kg i.p.) in rats was antagonized by caffeine and theophylline (10-50 mg/kg i.p.), and by selective adenosine A2 receptor antagonist (3,7-dimethyl-1-propargylxanthine) (3 and 6 mg/kg i.p.). Selective A1-adenosine receptor antagonist (8-cyclopentyltheophylline) (1.5 and 3 mg/kg i.p.) was not able to reduce this effect of haloperidol. These results confirm the antagonistic interaction between adenosine A2A and dopamine D2 receptors, and suggest the involvement of adenosine A2 receptors in the mechanisms of catalepsy.

Animals↗