Influence of oxcarbazepine on the antinociceptive action of morphine and metamizole in mice.

Numerous methods of management applied in order to obtain higher therapeutic efficacy of drugs with minimum adverse effects include taking advantage of interactions taking place between individual agents. Analgesics are combined with drugs belonging to other therapeutic groups, including, more and more frequently, antiepileptic agents. The influence of oxcarbazepine (10 mg/kg) on the antinociceptive effect of morphine (10 mg/kg) and metamizole (500 mg/kg) was investigated in mice using the hot-plate and tail-flick tests. All drugs were injected intraperitoneally (i.p.). Oxcarbazepine was administered 30 min prior to the injection of analgesic drugs. The reactions to noxious stimuli were measured 30, 60 and 90 min after the administration of an analgesic. The study was further conducted for 10 days with repeated drug doses. Single administration of oxcarbazepine enhanced the antinociceptive effect of a single dose of morphine, and 10-day administration led to a decrease of morphine tolerance in the hot-plate test. Oxcarbazepine administered in a single dose did not affect significantly the antinociceptive effect of metamizole in either of the tests. Multiple administration of oxcarbazepine enhanced the antinociceptive effect of metamizole in the hot-plate test. Oxcarbazepine alone, administered in a single and repeated doses, demonstrated an antinociceptive effect, but only for the hot-plate test, which indicates involvement of supraspinal structures in antinociception.

Synthesis and pharmacological evaluation of N-(dimethylamino)ethyl derivatives of benzo- and pyridopyridazinones.

New N-(dimethylamino)ethyl derivatives of phthalazinones and pyridopyridazinones 7, 9 were synthesized and assayed as potential analgesic agents in the hot-plate, tail-flick, and writhing tests. Pharmacological assay demonstrated that eight (in ten) of the newly synthesized compounds showed antinociceptive activity. Especially, 2-[2-(dimethylamino)ethyl]-4-phenyl-2H-phthalazin-1-one 7a showed remarkably higher antinociceptive activity in all tests. This is connected with influence on supraspinal, spinal, and peripheral structures. The decreased sensitivity to the pain stimulus in the hot-plate was higher than that of metamizole.

Influence of tiagabine on the antinociceptive action of morphine, metamizole and indomethacin in mice.

The influence of tiagabine at a dose of 3.2 mg/kg (single administration) and at a dose of 1.2 mg/kg (multiple administration - 10 days) on the antinociceptive effect of morphine (10 mg/kg), metamizole (500 mg/kg) and indomethacin (10 mg/kg - single dose and 1.4 mg/kg - multiple doses) was investigated in mice using the hot-plate and tail-flick tests. All drugs were injected intraperitoneally. Tiagabine was administered to mice 30 min before the analgesic drugs. Measurement of the reaction to a noxious stimulus was performed 60, 90 and 120 min after administration of tiagabine. The study was further conducted for 10 days with repeated drug doses. Tiagabine and morphine administered in single doses demonstrate an additive antinociceptive effect in the hot-plate test and a slightly synergistic effect in the tail-flick test. A single administration of tiagabine slightly increased the antinoceptive action of metamizole and indomethacin in both tests, but that effect is less pronounced than the antinociceptive action of tiagabine alone. Repeated administration of tiagabine with morphine abolishes the tolerance to morphine analgesia. Both single and repeated administration of tiagabine alone exerted the antinociceptive effect in the hot-plate test.

Synthesis and biological activity of N-methylated analogs of endomorphin-2.

In this paper, we describe the synthesis of a series of endomorphin-2 analogs containing N-methylated amino acids, consecutively in each position. The mu-opioid receptor binding affinities of the new analogs were determined in the displacement experiments. Their in vivo antinociceptive activity was assessed in the hot-plate test in mice after central (icv) and peripheral (ip) administration. [Sar2]endomorphin-2, which had the highest mu-receptor affinity, also showed the strongest analgesic effect when administered centrally and was the only analog that retained activity after peripheral injection.

Influence of sertraline on the antinociceptive effect of morphine, metamizol and indomethacin in mice.

Interaction between analgesic and various psychotropic drugs constitute a subject of many research investigations. Literature data considering this issue are often inconsistent. Sertraline is one of the most potent drugs in the family of selective serotonine reuptake inhibitors (SSRIs). The influence of sertraline (5 mg/kg) on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg or 1.4 mg/kg) was investigated in a mouse model using the tail-flick and hot-plate tests. All drugs were injected intraperitoneally. Sertraline was administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after sertraline administration. The research studies were futher conducted with multiple (14 days) drug dosage. Sertraline after single dose increased the antinociceptive effect of morphine (in the hot-plate test) and metamizol and indomethacin (only in the tail-flick test). Sertraline after 14 day administration decreased analgesic effect of morphine (only in the hot-plate test). Sertraline applied for 14 days increased the antinociceptive effect of indomethacin. Sertraline alone after multiple doses increased pain reaction time. The results of experiments suggest the role of sertraline in nociception and possibility of interaction between sertraline and analgesic drugs.

The effect of gabapentin on antinociceptive action of analgesics.

The effect of gabapentin at a dose of 10 mg/kg (single administration) and at 3 mg/kg/day (administered for 10 days) on the analgesic action of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg and 1.4 mg/kg) in mice was assessed on the basis of hot-plate and tail-flick tests. All the drugs were administered intraperitoneally (i.p.). Gabapentin was administered to mice 30 min before the administration of analgesics. The animals reactions to noxious stimuli were measured 60, 90 and 120 min after gabapentin administration. Gabapentin administered in a single dose, as well as in multiple ones, was found to cause antinociception, especially evident in the hot-plate test. The single dose of gabapentin enhances the analgesic effect of morphine in the hot-plate test, whereas in the tail-flick test it demonstrates an opposite effect. Gabapentin in a single dose does not affect significantly the effects of metamizol and indomethacin, whereas multiple doses decrease the action of these drugs. Gabapentin abolishes the tolerance of antinociceptive effect of morphine.

Influence of doxorubicin and carnosine on the standard 12-lead electrocardiogram in rabbits.

Doxorubicin (DOX) is an anthracycline antibiotic with a potent anticancer activity used against human neoplasms. Doxorubicin causes numerous adverse effects i.e., toxic effect on the cardiovascular system of experimental animals and humans. DOX may provoke a few types of cardiomyopathies: an acute, subacute, chronic and late-onset one. Changes in ECG can be observed at any stage of cardiovascular abnormalities. Abnormal ECG findings may initially be transient in character, whereas continued use of anthracyclines may lead to their fixation. ECG has been suggested as one of the methods allowing to detect cardiotoxicity of anthracycline antibiotics. The usefulness of ECG in assessment of anthracycline cardiotoxicity in experimental animals has been indicated by various authors. In our experiments, we wanted to find out whether carnosine (CAR)--a naturally occurring antioxidant, a dipeptide commonly occurring in the human organism, can influence the potential changes in standard ECG of DOX-treated rabbits, which could indicate its cardioprotective effect.

Influence of felbamate on the antinociceptive action of morphine, metamizol and indomethacin in mice.

The influence of felbamate (200 mg/kg or 50 mg/kg) on antinociceptive effect of morphine (10 mg/kg), metamizol (500 mg/kg) and indomethacin (10 mg/kg or 1.4 mg/kg) was investigated in a mouse model using the hot-plate test. All drugs were injected intraperitoneally. Felbamate was administered to mice 30 min before applying the analgesic drugs. Measurement of nociception was performed within 2 h after felbamate administration. The research studies were further conducted with a multiple (10 days) drug dosage. Felbamate in the dose of 200 mg/kg significantly increases the analgesic effect of morphine and weakens the effect of metamizol and indomethacin. Multiple administration of felbamate does not affect the activity of morphine and metamizol, but decreases analgesic effect of indomethacin.