The Experts below are selected from a list of 2577 Experts worldwide ranked by ideXlab platform
Gavin J Kilpatrick - One of the best experts on this subject based on the ideXlab platform.
-
Thioperamide the selective histamine h3 receptor antagonist attenuates stimulant induced locomotor activity in the mouse
European Journal of Pharmacology, 1994Co-Authors: Jane Clapham, Gavin J KilpatrickAbstract:Abstract The effects of the selective histamine H3 receptor agonist (R)-α-methylhistamine and antagonist Thioperamide on stimulant-induced locomotor activity in the mouse were examined. Amphetamine (1 mg·kg−1 s.c.), apomorphine (2 mg·kg−1 s.c.) or cocaine (5 mg·kg −1 s.c.) increased locomotor activity. Neither Thioperamide (10 mg·kg −1 i.p.) nor (R)-α-methylhistamine (20 mg·kg−1 i.p.) affected spontaneous locomotor activity in their own right. (R)-α-Methylhistamine (0.3, 3 or 20 mg·kg−1 i.p.) also had no effect on amphetamine (1 mg·kg −1 s.c.)-induced locomotor activity. In contrast, Thioperamide (0.2–10 mg·kg −1 i.p. or 0.3–20 μg i.c.v.) inhibited, in a dose-dependent manner, the hyperactivity response induced by amphetamine (1 mg·kg −1 s.c.). (R)-α-Methylhistamine (20 mg·kg −1 i.p.) completely reversed the inhibitory response to Thioperamide (2 mg·kg−1 i.p.). Thioperamide (2 or 10 mg·kg −1 i.p.) also inhibited apomorphine (2 mg·kg −1 s.c.)- and, to a lesser extent, cocaine (5 mg·kg−1 s.c.)-induced hyperactivity. We therefore conclude that antagonism of the central histamine H3 receptor inhibits, to a varying degree, the effects of locomotor stimulants.
-
Histamine H3 receptor-mediated modulation of water consumption in the rat
European journal of pharmacology, 1993Co-Authors: Jane Clapham, Gavin J KilpatrickAbstract:Abstract The effect of the selective H3 receptor agonist (R)-α-methylhistamine and antagonist Thioperamide on water consumption in the rat were examined. (R)-α-Methylhistamine (0.1–20 mg · kg−1 i.p.) evoked a dose-dependent increase in water consumption, the maximum effect being 310 ± 23% (n = 67) above the vehicle control response. Thioperamide (0.2,2 and 10 mg · kg−1 i.p.) alone had no effect on water consumption. However, the stimulatory effect of (R)-α-methylhistamine on water consumption was antagonised by Thioperamide in a dose-dependent manner, whereas the H1 receptor antagonist mepyramine and the H2 receptor antagonist loxtidine were without effect. It is therefore concluded that the H3 receptor may play a role in the regulation of water consumption in the rat.
-
histamine h3 receptors modulate the release of 3h acetylcholine from slices of rat entorhinal cortex evidence for the possible existence of h3 receptor subtypes
British Journal of Pharmacology, 1992Co-Authors: J Clapham, Gavin J KilpatrickAbstract:1. The effect of agents which interact with the histamine H3 receptor on potassium-stimulated tritium release from slices of rat entorhinal cortex preloaded with [3H]-choline is described. We have examined the effects of the selective H3 receptor agonist, (R)-alpha-methylhistamine (RAMH), and a number of H3 receptor antagonists, including the selective compound Thioperamide, on the potassium-stimulated release of tritium. 2. In the presence of mepyramine and ranitidine, RAMH (0.01-10 microM) inhibited potassium-stimulated tritium release in a concentration-dependent manner, EC50 = 0.11 microM. The maximum inhibition was approximately 50%. 3. Thioperamide displaced the RAMH concentration-response curve to the right yielding a pKB value of 8.4. There was no change in the maximum response to RAMH. 4. Other H3 receptor antagonists, including impromidine and burimamide, also caused rightwards displacement of the linear portion of the RAMH concentration-response curve. However, phenylbutanoylhistamine and betahistine, which are reported to be relatively potent H3 receptor antagonists, showed very low affinity. 5. Thioperamide (0.001-1 microM) alone enhanced the potassium-stimulated release of tritium in a concentration-dependent manner. Maximum effects were observed at 0.1-1 microM Thioperamide, enhancing release by approximately 20%. 6. Results are discussed in terms of the regulatory role of H3 receptors on acetylcholine release and the possible existence of H3 receptor subtypes.
-
In vivo occupancy of histamine H3 receptors by Thioperamide and (R)-α-methylhistamine measured using histamine turnover and an ex vivo labeling technique
Biochemical pharmacology, 1992Co-Authors: Simon J. Taylor, Anton D. Michel, Gavin J KilpatrickAbstract:Abstract In the brain, the H3 type of histamine receptor has a pre-synaptic autoreceptor inhibitory role which regulates neuronal release and synthesis of histamine. To examine the interaction of the selective H3 receptor antagonist Thioperamide with H3 receptors in the brain in vivo, we have used a functional and non-functional measurement of H3 receptor occupancy. In three species (rat, guinea-pig and mouse) peripheral administration of Thioperamide caused dose-related increases in histamine turnover in the cerebral cortex (whole brain was examined in the mouse) and, in the same tissues, inhibited the ex vivo binding of the selective H3 receptor agonist [ 3 H ](R)-α- methylhistamine ([ 3 H ]- RAMH ) . The peak effect of Thioperamide to inhibit ex vivo binding of [3H]RAMH was observed approximately 30 min after i.p. administration, whilst the maximum increase in histamine turnover did not occur until after at least 100 min. At a pretreatment time of 30 min, the ED50 of Thioperamide to inhibit ex vivo binding of [3H]RAMH binding in the rat, guinea-pig and mouse brain was found to be 2.0 ± 0.2, 4.8 ± 0.6 and 2.6 ± 0.3 mg/kg (mean ± SEM, N = 4), respectively. We have also examined the effect of peripheral administration of RAMH on ex vivo binding of [3H]RAMH in rat cortex. Qualitatively and quantitatively similar results to those of Thioperamide were observed following i.p. administration of RAMH to rats (ed50 = 3.9 ± 0.4 mg/kg, mean ± SEM, N = 4). An effect of RAMH on histamine turnover in rat cortex could not be determined as this compound displayed significant cross-reactivity with the antibodies used in the radioimmunoassay to measure histamine and telemethylhistamine. These data indicate that, following peripheral administration, both Thioperamide and RAMH penetrate the brain where they can subsequently interact with H3 receptors. It would appear that binding of Thioperamide to H3 receptors is linked with a concomitant increase in histamine turnover in the brain. In conclusion, the ex vivo binding technique, particularly when coupled with measurement of histamine turnover, should provide a valuable means for investigating the ability of any peripherally administered compound to cross the blood-brain barrier and subsequently interact with histamine H3 receptors.
Molly S. Griffith - One of the best experts on this subject based on the ideXlab platform.
-
Effects of the H_3 antagonist, Thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats
Psychopharmacology, 2009Co-Authors: Mark E. Bardgett, Megan Points, John Roflow, Meredith Blankenship, Molly S. GriffithAbstract:Rationale Recent studies have raised the possibility that antagonists of H_3 histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia. Objectives The purpose of this study was to determine if a prototypical H_3 antagonist, Thioperamide, could alter behavioral deficits caused by the N -methyl- d -aspartate (NMDA) receptor antagonist, MK-801, in adult male rats. MK-801 was chosen to be studied since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia. Methods The interaction between Thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or Thioperamide (3.0 and 10 mg/kg) followed 20 min later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, and 0.30 mg/kg). Results Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity; however, its impact on MK-801 was dose-dependent. Each Thioperamide dose enhanced the effects of two lower doses of MK-801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by Thioperamide pretreatment. Conclusions H_3 receptors modulate responses to NMDA antagonists in behaviorally specific and dose-dependent ways.
-
Effects of the H_3 antagonist, Thioperamide, on behavioral alterations induced by systemic MK-801 administration in rats
Psychopharmacology, 2009Co-Authors: Mark E. Bardgett, Megan Points, John Roflow, Meredith Blankenship, Molly S. GriffithAbstract:Rationale Recent studies have raised the possibility that antagonists of H_3 histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia. Objectives The purpose of this study was to determine if a prototypical H_3 antagonist, Thioperamide, could alter behavioral deficits caused by the N -methyl- d -aspartate (NMDA) receptor antagonist, MK-801, in adult male rats. MK-801 was chosen to be studied since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia. Methods The interaction between Thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or Thioperamide (3.0 and 10 mg/kg) followed 20 min later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, and 0.30 mg/kg). Results Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity; however, its impact on MK-801 was dose-dependent. Each Thioperamide dose enhanced the effects of two lower doses of MK-801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by Thioperamide pretreatment. Conclusions H_3 receptors modulate responses to NMDA antagonists in behaviorally specific and dose-dependent ways.
Roland Seifert - One of the best experts on this subject based on the ideXlab platform.
-
Mathematical analysis of the sodium sensitivity of the human histamine H_3 receptor
In Silico Pharmacology, 2014Co-Authors: Hans-joachim Wittmann, Roland Seifert, Andrea StrasserAbstract:Purpose It was shown by several experimental studies that some G protein coupled receptors (GPCR) are sensitive to sodium ions. Furthermore, mutagenesis studies or the determination of crystal structures of the adenosine A_2A or δ-opioid receptor revealed an allosteric Na^+ binding pocket near to the highly conserved Asp^2.50. Within a previous study, the influence of NaCl concentration onto the steady-state GTPase activity at the human histamine H_3 receptor (hH_3R) in presence of the endogenous histamine or the inverse agonist Thioperamide was analyzed. The purpose of the present study was to examine and quantify the Na^+-sensitivity of hH_3R on a molecular level. Methods To achieve this, we developed a set of equations, describing constitutive activity and the different ligand-receptor equilibria in absence or presence of sodium ions. Furthermore, in order to gain a better understanding of the ligand- and Na^+-binding to hH_3R on molecular level, we performed molecular dynamic (MD) simulations. Results The analysis of the previously determined experimental steady-state GTPase data with the set of equations presented within this study, reveals that Thioperamide binds into the orthosteric binding pocket of the hH_3R in absence or presence of a Na^+ in its allosteric binding site. However, the data suggest that Thioperamide binds preferentially into the hH_3R in absence of a sodium ion in its allosteric site. These experimental results were supported by MD simulations of Thioperamide in the binding pocket of the inactive hH_3R. Furthermore, the MD simulations revealed two different binding modes for Thioperamide in presence or absence of a Na^+ in its allosteric site. Conclusion The mathematical model presented within this study describes the experimental data regarding the Na^+-sensitivity of hH_3R in an excellent manner. Although the present study is focused onto the Na^+-sensitivity of the hH_3R, the resulting equations, describing Na^+- and ligand-binding to a GPCR, can be used for all other ion-sensitive GPCRs.
-
The dual H_3/4R antagonist Thioperamide does not fully mimic the effects of the ‘standard’ H_4R antagonist JNJ 7777120 in experimental murine asthma
Naunyn-Schmiedeberg's Archives of Pharmacology, 2013Co-Authors: Detlef Neumann, Silke Beermann, Heike Burhenne, Silke Glage, Christina Hartwig, Roland SeifertAbstract:Histamine is detected in high concentrations in the airways during an allergic asthma response. In a murine model of allergic asthma, the histamine H_4 receptor (H_4R)-selective ligand JNJ 7777120 reduces asthma-like symptoms. A sole antagonistic function of JNJ 7777120 at the murine H_4R has, however, been questioned in the literature. Therefore, in the present study, we aimed at analyzing the effects of JNJ 7777120 in comparison to that of the H_3/4R-selective antagonist Thioperamide. Experimental murine asthma was induced by sensitization and provocation of BALB/c mice with ovalbumine (OVA). JNJ 7777120, Thioperamide, or JNJ 5207852, an H_3R-selective antagonist which was used to dissect H_3R- and H_4R-mediated activities of Thioperamide, were injected subcutaneously during sensitization and effects were analyzed after provocation. Pharmacokinetic analyses revealed shortest t_1/2 values in both plasma and lung tissue and lowest maximal concentration in lung tissue for JNJ 7777120 in comparison to Thioperamide and JNJ 5207852. Nevertheless, JNJ 7777120 reduced serum titers of allergen-specific (anti-OVA) IgE, inflammatory infiltrations in lung tissue, and eosinophilia in bronchoalveolar lavage fluid. In contrast, Thioperamide reduced only eosinophilia in bronchoalveolar lavage fluid, while anti-OVA IgE concentrations and lung infiltrations remained unaffected. JNJ 5207852 had no effect on these parameters. JNJ 7777120 provides beneficial effects in experimental murine asthma, which, however, could only partially be mimicked by Thioperamide, despite more favorable pharmacokinetics. Thus, whether these effects of JNJ 7777120 are entirely attributable to an antagonistic activity at the murine H_4R or whether an agonistic activity is also involved has to be reconsidered.
-
The dual H3/4R antagonist Thioperamide does not fully mimic the effects of the 'standard' H4R antagonist JNJ 7777120 in experimental murine asthma.
Naunyn-Schmiedeberg's archives of pharmacology, 2013Co-Authors: Detlef Neumann, Silke Beermann, Heike Burhenne, Silke Glage, Christina Hartwig, Roland SeifertAbstract:Histamine is detected in high concentrations in the airways during an allergic asthma response. In a murine model of allergic asthma, the histamine H4 receptor (H4R)-selective ligand JNJ 7777120 reduces asthma-like symptoms. A sole antagonistic function of JNJ 7777120 at the murine H4R has, however, been questioned in the literature. Therefore, in the present study, we aimed at analyzing the effects of JNJ 7777120 in comparison to that of the H3/4R-selective antagonist Thioperamide. Experimental murine asthma was induced by sensitization and provocation of BALB/c mice with ovalbumine (OVA). JNJ 7777120, Thioperamide, or JNJ 5207852, an H3R-selective antagonist which was used to dissect H3R- and H4R-mediated activities of Thioperamide, were injected subcutaneously during sensitization and effects were analyzed after provocation. Pharmacokinetic analyses revealed shortest t1/2 values in both plasma and lung tissue and lowest maximal concentration in lung tissue for JNJ 7777120 in comparison to Thioperamide and JNJ 5207852. Nevertheless, JNJ 7777120 reduced serum titers of allergen-specific (anti-OVA) IgE, inflammatory infiltrations in lung tissue, and eosinophilia in bronchoalveolar lavage fluid. In contrast, Thioperamide reduced only eosinophilia in bronchoalveolar lavage fluid, while anti-OVA IgE concentrations and lung infiltrations remained unaffected. JNJ 5207852 had no effect on these parameters. JNJ 7777120 provides beneficial effects in experimental murine asthma, which, however, could only partially be mimicked by Thioperamide, despite more favorable pharmacokinetics. Thus, whether these effects of JNJ 7777120 are entirely attributable to an antagonistic activity at the murine H4R or whether an agonistic activity is also involved has to be reconsidered.
-
the dual h3 4r antagonist Thioperamide does not fully mimic the effects of the standard h4r antagonist jnj 7777120 in experimental murine asthma
Naunyn-schmiedebergs Archives of Pharmacology, 2013Co-Authors: Detlef Neumann, Silke Beermann, Heike Burhenne, Silke Glage, Christina Hartwig, Roland SeifertAbstract:Histamine is detected in high concentrations in the airways during an allergic asthma response. In a murine model of allergic asthma, the histamine H4 receptor (H4R)-selective ligand JNJ 7777120 reduces asthma-like symptoms. A sole antagonistic function of JNJ 7777120 at the murine H4R has, however, been questioned in the literature. Therefore, in the present study, we aimed at analyzing the effects of JNJ 7777120 in comparison to that of the H3/4R-selective antagonist Thioperamide. Experimental murine asthma was induced by sensitization and provocation of BALB/c mice with ovalbumine (OVA). JNJ 7777120, Thioperamide, or JNJ 5207852, an H3R-selective antagonist which was used to dissect H3R- and H4R-mediated activities of Thioperamide, were injected subcutaneously during sensitization and effects were analyzed after provocation. Pharmacokinetic analyses revealed shortest t1/2 values in both plasma and lung tissue and lowest maximal concentration in lung tissue for JNJ 7777120 in comparison to Thioperamide and JNJ 5207852. Nevertheless, JNJ 7777120 reduced serum titers of allergen-specific (anti-OVA) IgE, inflammatory infiltrations in lung tissue, and eosinophilia in bronchoalveolar lavage fluid. In contrast, Thioperamide reduced only eosinophilia in bronchoalveolar lavage fluid, while anti-OVA IgE concentrations and lung infiltrations remained unaffected. JNJ 5207852 had no effect on these parameters. JNJ 7777120 provides beneficial effects in experimental murine asthma, which, however, could only partially be mimicked by Thioperamide, despite more favorable pharmacokinetics. Thus, whether these effects of JNJ 7777120 are entirely attributable to an antagonistic activity at the murine H4R or whether an agonistic activity is also involved has to be reconsidered.
Giovanni Di Carlo - One of the best experts on this subject based on the ideXlab platform.
-
Histamine H3-receptor antagonism improves memory retention and reverses the cognitive deficit induced by scopolamine in a two-trial place recognition task
Behavioural brain research, 2001Co-Authors: Marco Orsetti, Piera Ghi, Giovanni Di CarloAbstract:Several reports have indicated that, under different experimental conditions, the administration of histamine H(3)-receptor antagonists exerts procognitive effects by activating central histaminergic transmission. In the present study the action of Thioperamide, a H(3)-receptor blocker, is investigated on consolidation and recall mechanisms of the rat place recognition memory. The animals have been tested on a two-trial delayed comparison paradigm in a Y-maze. Thioperamide enhances the memory retention when administered intraperitoneally (i.p.) post-acquisition (0.7 and 5.0 mg/kg are ineffective, whereas the dose of 2.0 mg/kg improves memory) but does not affect the rat performance when injected 45 min prior to the testing trial. The post-acquisition effect of Thioperamide is time-dependent since the administration of the drug 30 min after the end of the training trial has no effect on memory. In addition, Thioperamide reverses the amnesia induced by the post-acquisition treatment with 0.02 mg/kg i.p. of scopolamine (SCOP). The procognitive effect of Thioperamide is not modified by the contemporary administration of pyrilamine, an histamine H(1)-receptor antagonist. On the contrary, the blockade of H(2)-receptors by zolantidine 10 mg/kg reverses both the effect of Thioperamide alone and the drug action on the scopolamine-induced memory deficit. The results indicate that the neuronal histamine released in consequence of the post-acquisition Thioperamide treatment improves place recognition memory through the activation of postsynaptic H(2)-receptors.
-
Effect of R-(-)-α-methylhistamine and Thioperamide on in vivo release of norepinephrine in the rat hippocampus
Progress in neuro-psychopharmacology & biological psychiatry, 2000Co-Authors: Giovanni Di Carlo, Piera Ghi, Marco OrsettiAbstract:Abstract 1. 1. The modifications of hippocampal release of norepinephrine following the administration of R-(-)-α-methylhistamine and Thioperamide, respectively agonist and antagonist of histamine H 3 receptors, were assessed in freely moving rats by microdialysis. 2. 2. Both the systemic (2 mg/kg i.p.) and local (100 μM via the probe) administration of Thioperamide caused no modifications of basal release, indicating that the histaminergic system is not tonically involved in regulating the hippocampal noradrenergic activity. 3. 3. R-(-)-α-methylhistamine (1 and 100 μM) produced a slight, short-lasting and dose-dependent reduction of norepinephrine release antagonized by local perfusion (100 μM) and prevented by systemic administration of Thioperamide 2 mg/kg. 4. 4. The results seem to indicate that the modulation of norepinephrine release through presynaptic H 3 -receptors in the rat hippocampus plays a minor role in the memory-enhancing effects of Thioperamide.
-
combined action of Thioperamide plus scopolamine diphenhydramine or methysergide on memory in mice
Pharmacology Biochemistry and Behavior, 1999Co-Authors: Luigi Molinengo, Giovanni Di CarloAbstract:Abstract The aim of the present experiments was to test the role played by the interaction of the selective H 3 receptor antagonist, Thioperamide, with the cholinergic, histaminergic, and serotonergic systems in modifying memory. The behavioral tests used (open-field and passive-avoidance repetition) were selected on the basis of the action displayed by Thioperamide in these behavioral situations. Posttrial administration of Thioperamide (5 mg/kg) resulted in an improvement in memory consolidation, as tested in the repetition of the open-field test, but repeated posttrial administration of Thioperamide (2 or 5 mg/kg) had no effect in the repetition of passive avoidance test. Scopolamine (2 mg/kg) caused a deterioration in the memory processes in both tests; this effect was blocked by 2 mg/kg of Thioperamide, which was itself ineffective in the test. These results may suggest that both the improvement in memory due to Thioperamide and its antagonism of the amnestic effects of scopolamine are determined by activation of central cholinergic systems, due to Thioperamide inhibition of H 3 heteroreceptors. Diphenhydramine (2 or 10 mg/kg) was itself ineffective in the tests, but counteracted the memory improvement caused by Thioperamide in the repetition of the open-field test. The effect of diphenhydramine is discussed in terms of interactions between histaminergic and cholinergic systems. Methysergide counteracted the effect of Thioperamide in the open-field test only at a high dosage (50 mg/kg). The possible implication of serotonergic systems on the effects of the methysergide–Thioperamide interaction in the memory process is discussed.
-
Effects of Thioperamide on locomotor activity and on memory processes.
Progress in neuro-psychopharmacology & biological psychiatry, 1998Co-Authors: Piera Ghi, Giovanni Di Carlo, Luigi MolinengoAbstract:Abstract 1. 1. Rats were tested in an open field. Thioperamide given ip. 30 minutes before the tests produced an increase of locomotor activity at 2 mg/kg and no behavioral effect at 5 mg/kg. 2. 2. The repetition of the open field tests caused a reduction of ambulation in three successive tests. This effect was increased by Thioperamide 2 and 5 mg/kg given after the tests, suggesting that this compound improved memory consolidation.
Kenji Onodera - One of the best experts on this subject based on the ideXlab platform.
-
effects of Thioperamide a histamine h3 receptor antagonist on a scopolamine induced learning deficit using an elevated plus maze test in mice
Life Sciences, 1995Co-Authors: S Miyazaki, Masahiro Imaizumi, Kenji OnoderaAbstract:We examined the effects of Thioperamide and (R)-α-methylhistamine, a histamine H3-receptor antagonist and an agonist, respectively, on a scopolamine-induced learning deficit using an elevated plus-maze test in mice. Thioperamide alone slightly improved the learning deficit induced by scopolamine, and pretreatment with zolantidine, a histamine H2-receptor antagonist, significantly enhanced the effect of Thioperamide in this test. (R)-α-Methylhistamine, pyrilamine, ketotifen, terfenadine, and zolantidine alone at the doses tested had no effect. Moreover, the improvement by Thioperamide plus zolantidine was antagonized by pretreatment with histamine H1-receptor antagonists such as pyrilamine or ketotifen, but not by terfenadine. Thus, Thioperamide improved the scopolamine-induced learning deficit through central histamine H1 receptors in mice. The present results supported the hypothesis that histamine may play an important role in learning and memory.
-
The differential effects of histamine receptor antagonists on morphine- and U-50,488H-induced antinociception in the mouse.
Life sciences, 1994Co-Authors: Tsutomu Suzuki, Kazuaki Takamori, Yuki Takahashi, Minoru Narita, Miwa Misawa, Kenji OnoderaAbstract:The effects of Thioperamide, an H3 antagonist, and histamine H1 and H2 antagonists (s.c.) on morphine (s.c. or i.c.v.)- and U-50,488H (i.c.v.)-induced antinociception in male ddY mice were examined using the hot-plate (55 degrees C) test. Thioperamide significantly inhibited morphine-induced antinociception, but not U-50,488H-induced antinociception. The suppressive effect of Thioperamide on morphine-induced antinociception was reversed by the H1 antagonist pyrilamine, but not by the H2 antagonist zolantidine. On the other hand, pyrilamine significantly potentiated the antinociception induced by morphine, but not that induced by U-50,488H. Zolantidine significantly inhibited morphine-induced antinociception in a dose-dependent manner, but not U-50,488H-induced antinociception. Both astemizole, an H1 antagonist, and ranitidine, an H2 antagonist, which are known to barely cross the blood brain barrier, did not affect morphine-induced antinociception. These results suggest that morphine-induced antinociception may be potentiated by activation of H2 receptors and suppressed by activation of H1 receptors in the brain. Furthermore, neuronal histamine release induced by Thioperamide may suppress morphine-induced antinociception through H1 receptors.
-
effect of Thioperamide a histamine h3 receptor antagonist on electrically induced convulsions in mice
European Journal of Pharmacology, 1993Co-Authors: Hiroyuki Yokoyama, Kazuie Iinuma, Kenji Onodera, Takehiko WatanabeAbstract:Abstract The effect of Thioperamide, a histamine H 3 receptor antagonist, on electrically induced convulsions was studied in mice. Thioperamide significantly and dose dependently decreased the duration of each phase of convulsion and raised the electroconvulsive threshold. Its anticonvulsant effects were prevented by pretreatment with (R)-α-methylhistamine, a histamine H 3 receptor agonist. These findings suggest that the effect of Thioperamide on electrically induced convulsions is due to an increase in endogenous histamine release in the brain, an effect mediated by histamine H 3 receptors. The anticonvulsant effect of Thioperamide was antagonized strongly by mepyramine (or pyrilamine), a centrally acting histamine H 1 receptor antagonist, but not by zolantidine, a centrally acting histamine H 2 receptor antagonist. Thus, the blockade by mepyramine of the Thioperamide-induced decrease in seizure susceptibility indicates that histamine released by Thioperamide from the histaminergic nerve terminals interacts with the histamine H 1 receptors of postsynaptic neurons. These findings support the hypothesis that the central histaminergic system is involved in the inhibition of seizures.
-
the behavioral and biochemical effects of Thioperamide a histamine h3 receptor antagonist in a light dark test measuring anxiety in mice
Life Sciences, 1993Co-Authors: Masahiro Imaizumi, Kenji OnoderaAbstract:Abstract We investigated the effects of Thioperamide, a histamine H 3 -receptor antagonist, in a light/dark test measuring anxiety in mice. Thioperamide (20 mg/kg) slightly affected the locomotion and time spent in a light zone, and shuttle crossing. However, the decreases of these parameters were significant only when the animals were pretreated with zolantidine, a histamine H 2 -receptor antagonist. Moreover, the decreased parameters induced by the combination of Thioperamide and zolantidine were reversed by pretreatment with pyrilamine, a histamine H 1 -receptor antagonist. These data suggest that Thioperamide induces the release of neuronal histamine, which in turn stimulates both H 1 - and H 2 -receptors to produce the anxiogenic effect. The stimulation of histamine H 1 -receptors may mediate the anxiety, while H 2 -receptors may play a role in masking the anxiogenic effect. Thus, the present study suggests the involvement of endogenous neuronal brain histamine in anxiety. In the biochemical study, a previous report showed that Thioperamide accelerated the release of neuronal histamine in the brains of mice [Sakai et al., Life Sciences, 48 , 2397–2404(1991)]. This study also demonstrated that Thioperamide did not affect the turnover rate of noradrenaline, dopamine, or serotonin in the brains of mice, which indicates that Thioperamide is a good pharmacological tool for accelerating the release of neuronal histamine in the brain.
-
The behavioral and biochemical effects of Thioperamide, a histamine H3-receptor antagonist, in a light/dark test measuring anxiety in mice
Life sciences, 1993Co-Authors: Kenji OnoderaAbstract:Abstract We investigated the effects of Thioperamide, a histamine H 3 -receptor antagonist, in a light/dark test measuring anxiety in mice. Thioperamide (20 mg/kg) slightly affected the locomotion and time spent in a light zone, and shuttle crossing. However, the decreases of these parameters were significant only when the animals were pretreated with zolantidine, a histamine H 2 -receptor antagonist. Moreover, the decreased parameters induced by the combination of Thioperamide and zolantidine were reversed by pretreatment with pyrilamine, a histamine H 1 -receptor antagonist. These data suggest that Thioperamide induces the release of neuronal histamine, which in turn stimulates both H 1 - and H 2 -receptors to produce the anxiogenic effect. The stimulation of histamine H 1 -receptors may mediate the anxiety, while H 2 -receptors may play a role in masking the anxiogenic effect. Thus, the present study suggests the involvement of endogenous neuronal brain histamine in anxiety. In the biochemical study, a previous report showed that Thioperamide accelerated the release of neuronal histamine in the brains of mice [Sakai et al., Life Sciences, 48 , 2397–2404(1991)]. This study also demonstrated that Thioperamide did not affect the turnover rate of noradrenaline, dopamine, or serotonin in the brains of mice, which indicates that Thioperamide is a good pharmacological tool for accelerating the release of neuronal histamine in the brain.
