Effect of Agrimonia pilosa Ledeb Extract on the Antinociception and Mechanisms in Mouse

In the present study, the antinociceptive profiles of Agrimonia pilosa Ledeb extract were examined in ICR mice. Agrimonia pilosa Ledeb extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Agrimonia pilosa Ledeb extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microg) was diminished by Agrimonia pilosa Ledeb extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Agrimonia pilosa Ledeb extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Agrimonia pilosa Ledeb extract in the writhing test. Our results suggest that Agrimonia pilosa Ledeb extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Agrimonia pilosa Ledeb extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.

Antinociception Effect and Mechanisms of Campanula Punctata Extract in the Mouse

In the present study, the antinociceptive profiles of Campanula punctata extract were examined in ICR mice. The Campanula punctata contain a large dose of saponin. Campanula punctata extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Campanula punctata extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P (0.7 microgram) was diminished by Campanula punctata extract. Intraperitoneal (i.p.) pretreatment with yohimbine (alpha2-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Campanula punctata extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Campanula punctata extract in the writhing test. Our results suggest that Campanula punctata extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Campanula punctata extract may be mediated by alpha2-adrenergic receptor, but not opioidergic and serotonergic receptors.

Tramadol, Alpha-2 Adrenalin Receptor Subtype and Neuropathic Rat Model / 대한마취과학회지

BACKGROUND: Spinally administered alpha(2)-adrenergic agonists show analgesic effects in normal and neuropathic states. Their effects are mediated via alpha(2)-adrenoceptors. Plasticity of nervous system after nerve injury can change the expressions of the related receptors in spinal cord. The expression of alpha(2)-adrenoceptor subtypes in spinal cord and the effect of chronic systemic administration of tramadol was probed in neuropathic rat pain model. METHODS: Sprague-Dawley rats were prepared to make neuropathic pain model by L5 and L6 spinal nerve ligation. Withdrawal threshold for tactile allodynia was evaluated with von Frey hair throughout experiment. Tramadol (15 mg/kg) or equivalent volume of saline was injected intraperitoneally twice a day for 21 days. In the 14th day and 21st day, allodynia and the systemic effect of tramadol was measured and compared with control group. At the 21st day, rat spinal cords were harvested and the expression of alpha(2)-adrenoceptor subtypes were measured and compared with real time PCR. RESULTS: Chronic administration of tramadol did not improve the allodynia nor the effect of tramadol in spinal nerve ligation model. The mRNA of alpha(2A)-adrenoceptor in nerve injury site decreased compared to controlateral site. The mRNA of alpha(2C)-adrenoceptor subtype in nerve injury rat decreased compared with normal animal, and chronic administration of tramadol increased it compared to saline group. CONCLUSIONS: Rats with neuropathic pain by spinal nerve ligation showed the expression of alpha(2)-adrenoceptors subtypes in spinal cord, and chronic systemic administration of tramadol may influence the expression of alpha(2)-adrenoceptors subtypes.

Monoaminergic Activity by Drugs Acting on Adrenergic alpha2-receptors in Rat Hippocampus and Primary Visual Cortex / 대한정신약물학회지

OBJECTIVE: The aim of the this study was to compare the effects of clonidine (a alpha2-adrenoceptor and imidazoline receptor agonist), yohimbine (a selective alpha2-adrenoceptor antagonist) and idazoxan (a alpha2-adrenoceptor and imidazoline receptor antagonist) on extracellular monoamines and their metabolites by using the awakening animal microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in brain regions, which are suggested to have regulatory role in depression. METHODS: We used intracerebral microdialysis in awakening rats by inserting probe through the dorsal hippocampus and occipital cortex especially in primary visual cortex, We studied respective effects of 2.0 mg/kg of clonidine, 5.0 mg/kg of yohimbine, and 5.0 mg/kg of idazoxan on the release of MHPG (a major metabolite of norepinephrine), norepinephrine (NE), DOPAC (a major metabolite of dopamine), and 5-HIAA (a main metabolite of serotonin) by intraperitoneal administration. RESULTS: Clonidine decreased the release of MHPG, NE, DOPAC, and 5-HIAA in both dorsal hippocampus and occipital cortex regions, and there were no significant differences in releasing pattern of all monoamines and their metabolites. Both yohimbine and idazoxan enhanced the release of MHPG, NE, DOPAC, and 5-HIAA in both brain regions, but there were significant differences in releasing pattern of NE and 5-HIAA. Idazoxan induced the delayed and higher efflux of NE and 5-HIAA in the primary visual cortex than yohimbine, but not in the hippocampus. CONCLUSION: This study shows that the selective alpha2-adrenoceptor antagonists increase basal monoamine output and enhance the metabolism of them in the hippocampus and primary visual cortex, and the imidazoline receptor has modulatory role in the regulation of monoamine release in primary visual cortex than hippocampus. It also suggests that high turnover rate of serotonin and norepinephrine in primary visual cortex may contribute to the pathophysiological role in depression.

Relationship between Central alpha2-Adrenoceptors and Pressor Response to Raised Intracranial Pressure in Rabbits

The effects of intraventricular alpha2-adrenoceptor agonist and antagonist, clonidine and rauwolscine, on changes of blood pressure induced by the rise of intracranial pressure were investigated in urethane-anesthetized rabbits. 2) The rise of ICP, induced by the infusion of saline into a balloon placed in the epidural space, was comparatively slow in the beginning of the infusion but became sharp as the infusion proceeded. Corresponding with the gradual increase of ICP, there was a slight decrease in BP. An abrupt rise of BP was observed when ICP showed a sharp increase. 3) Intraventricular rauwolscine 5(microgram) by itself did not affect BP. In these rauwolscine-treated rabbits the increase of both ICP and BP by the infusion was similar to that of the control animals. 4) The pretreatment with rauwolscine 50(microgram) did hardly affect BP, but this made the increase of ICP and BP by the infusion different from that of the control animals. The slight hypotensive response in the beginning of the infusion did not appear and the pressor response to the raised ICP was markedly facilitated. The volume of saline inused into the infusing balloon to cause the same increase of ICP as in the control animals was much smaller than in the control ones, and the magnitude of the maximal increase of BP was much greater. 5) The pretreatment with 500 microgram of intraventricular rauwolscine produced an increase of BP. In these animals the increase of both ICP and BP by the infusion seemed to be slightly facilitated than in the control animals. 6) Intraventricular clonidine 30(microgram) markedly decreased BP. In these clonidine-treated animals the slight hypotensive response in the beginning was more distinct than in the control animals, and the pressor response was hardly seen. 7) The hypotensive response to intraventricular clonidine 30(microgram) was weakened in the animals pretreated with intraventricular rauwolscine 500(microgram). In these animals the increase of both ICP and BP by the infusion appeared as in the control animals. 8) The above results suggest that the pressor response to the raised ICP in rabbits was inhibited under the condition of stimulation of central alpha2-adrenoceptors and facilitated under the condition of blockade of the receptors. It seems that the rise of blood pressure takes place when the activity of alpha2-adrenoceptors is impared by the increased pressure of the balloon placed in the epidural space.

The Relationship Between Increased Intracranial Pressure and Central alpha-Adrenoceptors

The author attempted to clarify the nature of alpha-adrenoceptors in relation to the pressor response to the increased intracranial pressure(ICP) in urethane-anesthetized rabbits, using the epidural balloon method. 1) The blood pressure increased in parallel with the raised ICP which was made by gradual inflation of the balloon. 2) B-HT 920, an alpha2-agonist, which elicited depressor and bradycardiac responses in normal rabbits inhibited markedly the pressor response to the raised ICP. 3) Piperoxan, an alpha2-antagonist, potentiated the pressor response to the raised ICP. 4) Piperoxan antagonized the depressor and bradycardiac responses by B-HT 920 as well as the inhibitory effect of B-HT 920 on the pressor response to the raised ICP. 5) The pressor response to the raised ICP were not affected at all by prazosin, an alpha1-antagonist. 6) Neither the depressor and bradycardiac responses by B-HT 920 itself nor the inhibitory effect of B-HT 920 on the pressor response to the raised ICP were significantly affected by prazosin. It is inferred from these observations that the central alpha-adrenoceptors play an important role in producing the pressor response to the raised ICP and that the receptors involved here seems to be of alpha2-type.

The Relationship Between Increased Intracranial Pressure and Central alpha-Adrenoceptors

The author attempted to clarify the nature of alpha-adrenoceptors in relation to the pressor response to the increased intracranial pressure(ICP) in urethane-anesthetized rabbits, using the epidural balloon method. 1) The blood pressure increased in parallel with the raised ICP which was made by gradual inflation of the balloon. 2) B-HT 920, an alpha2-agonist, which elicited depressor and bradycardiac responses in normal rabbits inhibited markedly the pressor response to the raised ICP. 3) Piperoxan, an alpha2-antagonist, potentiated the pressor response to the raised ICP. 4) Piperoxan antagonized the depressor and bradycardiac responses by B-HT 920 as well as the inhibitory effect of B-HT 920 on the pressor response to the raised ICP. 5) The pressor response to the raised ICP were not affected at all by prazosin, an alpha1-antagonist. 6) Neither the depressor and bradycardiac responses by B-HT 920 itself nor the inhibitory effect of B-HT 920 on the pressor response to the raised ICP were significantly affected by prazosin. It is inferred from these observations that the central alpha-adrenoceptors play an important role in producing the pressor response to the raised ICP and that the receptors involved here seems to be of alpha2-type.