Study of antiseizure effects of Matricaria recutita extract in mice.

Matricaria recutita L. is a well-known medicinal plant that is suggested as being carminative, analgesic, and anticonvulsant in traditional medicine. In the present investigation the effect of hydro-methanolic percolated extract of this plant on seizure induced by picrotoxin was studied in male mice. This study was performed on animals pretreated with doses of 100, 200, and 300 mg/kg of extract or 40 mg/kg phenobarbital as the reference drug via intraperitoneal injection. After 20 min each animal received 12 mg/kg picrotoxin for induction of seizure. Latency of onset time of seizure, duration of seizure, death latency, and death rate were determined in experimental and control groups. The results showed that latency of the beginning time of seizure was increased in groups that were pretreated with different doses of extract. The most effective dose was 200 mg/kg (P < 0.05). In addition, this dose delayed the time of death in mice (P < 0.01). The extract had no effect on the death rate. The results indicate that the extract of M. recutita possesses suitable effects on seizure induced by picrotoxin, and more experiments are needed in this field.

Evaluation of anti-inflammatory and analgesic activity of a novel rigid 3, 4-dihydroxy chalcone in mice.

There have been many reports indicating the analgesic and anti-inflammatory effects of 3,4-dihydroxychalcones. We have designed and synthesized a rigid 3,4-dihydroxychalcone (RDHC) as a possible drug effecting inflammation and nociception. The analgesic and anti-inflammatory effects were evaluated by formalin and hot-plate tests, respectively. The results showed that RDHC induced significant antinociceptive and anti-inflammatory effects (P < 0.01). Maximum analgesia (63.7%) was observed at 37.5 mg/kg in the first phase of the formalin test. The effect of RDHC was higher in the chronic phase (inflammation phase) of the formalin test (86.4%, P < 0.01). In addition, a significant analgesia (maximum possible effect; MPE = 30.1%) was observed in the hot plate test 45 min after injection of 37.5 mg/kg RDHC (P < 0.01). As a result of our findings, this new RDHC could be suggested for further pharmacological studies.

The analgesic effect of Tribulus terrestris extract and comparison of gastric ulcerogenicity of the extract with indomethacine in animal experiments.

Tribulus terrestris has been used in traditional medicine for relieving rheumatic pain and as an analgesic plant for a long time. In this investigation the analgesic effect of methanolic extract of this plant on male albino mice was evaluated by formalin and tail flick test. Extraction of the fruits of the plant was done by two different methods (suxheletion and percolation) with methanol 80%. The percolated extract was injected intraperitoneally in mice at 50, 100, 200, 400, and 800 mg/kg. The results showed that a dose of 100 mg/kg of percolated extract had the highest significant analgesic effect compared to the control group (P < 0.01) in formalin and tail flick test. There is no significant difference in the analgesic effect of suxheleted and percolated extract. The analgesic effect of the extract was lower than morphine, 2.5 mg/kg in both tests, and higher than ASA 300 mg/kg in chronic phase of pain in formalin test (P < 0.05). Pretreatment of animal with naloxone did not change the analgesia induced by the plant extract in both tests, therefore the involvement of opioid receptor in the analgesic effect of this plant was excluded. The results of ulcerogenic studies indicate that the gastric ulcerogenecity of plant extract is lower than the indomethacin in the rat's stomach. It can therefore be concluded that T. terrestris extract has a suitable analgesic effect and further studies are required to produce a more effective product of this plant to substitute for conventional analgesic drugs.

Effect of adenosine receptor agonists and antagonists on morphine-induced catalepsy in mice.

Effects of adenosine receptor agonists and antagonists on morphine-induced catalepsy in mice were investigated. The adenosine agonists, NECA (5'-N-ethylcarboxamidoadenosine) and S-PIA (S(+)-N6-(2-phenylisopropyl)adenosine) in doses which did not induce any response, increased the cataleptogenic effect produced by morphine. However, the morphine response was decreased and increased by the lower and higher doses of the adenosine receptor agonist, CHA (N6-cyclohexyladenosine), respectively. The adenosine receptor antagonist, theophylline, decreased, but 8-phenyltheophylline increased, the response induced by morphine. Naloxone inhibited the catalepsy induced by morphine or morphine + NECA but not that induced by NECA alone. It is concluded that adenosine A2 receptor activation increases, while adenosine A1 receptor stimulation decreases, the morphine cataleptogenic response. The response to morphine may be mediated through opioid and adenosine receptor mechanisms.

Effect of picrotoxin on antinociception in the formalin test.

Subcutaneous injection of diluted formalin (0.25 microliter of 0.5%) caused a biphasic pain response in mice. The first phase of pain was observed during the first 5 min., while the second phase occurred 10-30 min. after formalin administration. With the formalin test, it was found that the antinociception produced by the GABA-A antagonist, picrotoxin, and the GABA-B antagonist, phaclofen, was abolished when employed in combination. The opioid antagonist naloxone and antimuscarinic atropine also decreased the picrotoxin response. However, sulpiride, SCH 23390, phenoxybenzamine and propranolol did not alter the picrotoxin response. Administration of naloxone, sulpiride and propranolol showed a pain response. The data indicate that dopaminergic and adrenergic mechanisms may not be involved in the picrotoxin antinociceptive effect. However, postsynaptic GABA-A and GABA-B may be involved in the drug effect, and involvement of opioid or cholinergic systems can not be excluded.

On the mechanisms by which theophylline changes core body temperature in mice.

In the present work, the effects of neurotransmitter antagonists on theophylline-induced changes in body temperature were investigated. Intraperitoneal (i.p.) administration of a low dose of theophylline (25 mg/kg) induced slight hyperthermia, while high doses (75 and 100 mg/kg) induced hypothermia. The hypothermic effect of theophylline was decreased by pretreatment of animals with the dopamine D2 receptor antagonists sulpiride (15 and 30 mg/kg i.p.) and pimozide (0.125 and 0.25 mg/kg i.p.), the muscarinic receptor antagonist atropine (2.5 and 5 mg/kg i.p.) and the 5-HT receptor antagonist metergoline (0.25 mg/kg i.p.). However, the dopamine D1 receptor antagonist SCH 23390 (0.05 and 0.5 mg/kg i.p.), the alpha-adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg i.p.) did not after the theophylline response. In reserpinized mice, theophylline caused a dose-dependent rise in body temperature. The response was blocked in animals pretreated with phenoxybenzamine, propranolol and atropine. Single treatment of animals with either SCH 23390 or sulpiride, and also with a combination of the two drugs, decreased the hyperthermia induced by theophylline in reserpinized mice. Pimozide or metergoline did not have any effect in this respect. These data suggest that the hypothermic response to theophylline may be mediated through dopaminergic, cholinergic and serotonergic mechanisms. The hyperthermic action of theophylline in reserpinized animals may be mediated through dopaminergic, cholinergic and adrenergic systems. Overall it seems likely that theophylline interacts with modulatory mechanisms involved in thermoregulation.

On the mechanism(s) of morphine-induced hypothermia.

The effects of morphine on core body temperature of mice in the presence or absence of catecholamine receptor antagonists were examined. Administration of different doses of morphine (20, 30 and 40 mg/kg) to mice caused a hypothermic effect. Pre-treatment of animals with the opioid receptor antagonist naloxone (1, 1.5 and 3 mg/kg), the D-2 receptor antagonists sulpiride (25 and 50 mg/kg), pimozide (0.0625, 0.125 and 0.25 mg/kg) and the adenosine receptor antagonist theophylline (25 and 50 mg/kg) decreased the morphine-induced hypothermia. The D-1 receptor antagonist SCH 23390 (0.1 and 0.2 mg/kg), the peripheral D-2 antagonist domperidone (10 and 30 mg/kg), the serotonin (5-HT) antagonist methysergide (5 and 10 mg/kg), the adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg) and the ß-adrenoceptor antagonist propranolol (5 and 10 mg/kg) did not inhibit the morphine response. The antimuscarinic drug atropine (5 and 10 mg/kg) caused a slight decrease in the morphine response. In animals pre-treated with reserpine (5 mg/kg), a hyperthermic response was observed after morphine injection. It is concluded that indirect dopaminergic or adenosine receptor mechanism(s) may be involved in the morphine-induced hypothermia in mice.

Involvement of adenosine receptors in mouse thermoregulation.

The effects of the activation of adenosine receptors on core body temperature of mice have been studied in the present investigation. Intraperitoneal (i.p.) injection of non-selective adenosine agonists 5'-N ethyl- carboxamide adenosine (NECA; 0.001, 0.01 and 0.05 mg/kg), R-(N(6)-phenylisopropyl)-adenosine (R-PIA; 0.01, 0.1 and 0.25 mg/kg) and selective A(1) adenosine agonist N(6)-cyclohexyladenosine (CHA; 0.1, 0.25 and 0.4 mg/kg) reduced core body temperature. However, R-PIA and CHA were less potent than NECA in reducing the core body temperature. Theophylline (12.5, 25 and 50 mg/kg) blocked the hypothermia of the adenosine agonists. Pre-treatment of animals with selective A(1) adenosine antagonist 8-phenyltheophylline (8-PT; 0.5, 1 and 2 mg/kg) decreased the hypothermic response of CHA but not of NECA and R-PIA. 8-PT potentiated the hypothermia induced by R-PIA. These results suggest that activation of both A(1) and A(2) adenosine receptors decreases core body temperature in mice.