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Junzo Kamei - One of the best experts on this subject based on the ideXlab platform.
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Antitussive effect of WIN 55212-2, a cannabinoid receptor agonist.
European journal of pharmacology, 2003Co-Authors: Kayo Morita, Junzo KameiAbstract:Several lines of evidence indicate that the opioid and cannabinoid systems produce synergistic interactions. The present study examined the opioid receptors involved in the antitussive effect of WIN 55212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate), a high-affinity cannabinoid receptor agonist, in mice. WIN 55212-2, at doses of 0.3-3 mg/kg ip, produced a dose-dependent antitussive effect. This antitussive effect of WIN 55212-2 was antagonized by pretreatment with either methysergide (3 mg/kg ip), a 5-HT receptor antagonist, or naloxone (1 mg/kg ip), an opioid receptor antagonist. Furthermore, pretreatment with N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A, 3 mg/kg ip), a cannabinoid CB(1) receptor antagonist, also significantly reduced the antitussive effect of WIN 55212-2. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine (40 mg/kg sc) significantly reduced the antitussive effect of WIN 55212-2. However, pretreatment with nor-binaltorphimine (20 mg/kg sc), a kappa-opioid receptor antagonist, did not affect the antitussive effect of WIN 55212-2. Pretreatment with naloxonazine (35 mg/kg sc), a mu(1)-opioid receptor antagonist, also did not affect the antitussive effect of WIN 55212-2. These results indicate that the antitussive effect of WIN 55212-2 is mediated by the activation of cannabinoid CB(1) receptors and mu(2) (naloxonazine-insensitive)-opioid receptors, but not mu(1) (naloxonazine-sensitive)- or kappa-opioid receptors.
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Antitussive effect of WIN 55212-2, a cannabinoid receptor agonist.
European Journal of Pharmacology, 2003Co-Authors: Kayo Morita, Junzo KameiAbstract:Abstract Several lines of evidence indicate that the opioid and cannabinoid systems produce synergistic interactions. The present study examined the opioid receptors involved in the antitussive effect of WIN 55212-2 (( R )-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate), a high-affinity cannabinoid receptor agonist, in mice. WIN 55212-2, at doses of 0.3–3 mg/kg ip, produced a dose-dependent antitussive effect. This antitussive effect of WIN 55212-2 was antagonized by pretreatment with either methysergide (3 mg/kg ip), a 5-HT receptor antagonist, or naloxone (1 mg/kg ip), an opioid receptor antagonist. Furthermore, pretreatment with N -(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H -pyrazole-3-carboxamide hydrochloride (SR141716A, 3 mg/kg ip), a cannabinoid CB 1 receptor antagonist, also significantly reduced the antitussive effect of WIN 55212-2. Blockade of μ-opioid receptors by pretreatment with β-funaltrexamine (40 mg/kg sc) significantly reduced the antitussive effect of WIN 55212-2. However, pretreatment with nor-binaltorphimine (20 mg/kg sc), a κ-opioid receptor antagonist, did not affect the antitussive effect of WIN 55212-2. Pretreatment with naloxonazine (35 mg/kg sc), a μ 1 -opioid receptor antagonist, also did not affect the antitussive effect of WIN 55212-2. These results indicate that the antitussive effect of WIN 55212-2 is mediated by the activation of cannabinoid CB 1 receptors and μ 2 (naloxonazine-insensitive)-opioid receptors, but not μ 1 (naloxonazine-sensitive)- or κ-opioid receptors.
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Antitussive principles of Glycyrrhizae radix, a main component of the Kampo preparations Bakumondo-to (Mai-men-dong-tang).
European journal of pharmacology, 2003Co-Authors: Junzo Kamei, Rie Nakamura, Hiroyuki Ichiki, Masayoshi KuboAbstract:We attempted to elucidate the antitussive principles of Glycyrrhizae radix, a main component of Bakumondo-to (Mai-men-dong-tang). Although the 50% methanol-eluted fraction (100 mg/kg, p.o.) caused a more than 60% reduction in the number of capsaicin-induced coughs, neither the water-eluted nor 100% ethanol-eluted fractions of water extract of G. radix had antitussive effects. The water extract of G. radix contained high levels of liquiritin, liquiritin apioside, isoliquiritin, isoliquiritin apioside and glycyrrhizin. On the other hand, the 50% methanol-eluted fraction contained mainly liquiritin and liquiritin apioside, but not the other compounds. Liquiritin apioside (3-30 mg/kg, p.o.), but not liquiritin, isoliquiritin, isoliquiritin apioside or glycyrrhizin, dose-dependently inhibited the number of coughs. Methysergide, a serotonin receptor antagonist, antagonized the antitussive effect of liquiritin apioside. However, the antitussive effect of liquiritin apioside was not antagonized by naloxone. Pretreatment with glibenclamide (3 mg/kg, i.p.), an ATP-sensitive potassium channel blocker, also significantly reduced the antinociceptive effect of liquiritin apioside. These results suggest that G. radix contains a potent antitussive compound, liquilitin apioside, whose antitussive effect may depend on both peripheral and central mechanisms.
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Inhaled pinacidil, an ATP-sensitive K+ channel opener, and moguisteine have potent antitussive effects in guinea pigs.
Japanese Journal of Pharmacology, 2002Co-Authors: Kayo Morita, Kenji Onodera, Junzo KameiAbstract:Abstract We investigated whether inhaled pinacidil and moguisteine inhibit capsaicin-induced coughs in guinea pigs. Inhaled pinacidil (15-60 μ g / ml), an ATP-sensitive K+ channel opener, and moguisteine (15-60 μ g / ml) each dose-dependently inhibited the number of capsaicin-induced coughs. The antitussive effects of pinacidil and moguisteine were significantly antagonized by pretreatment with glibenclamide (10 mg /kg, i.p.), an ATP-sensitive K+ channel blocker. However, pretreatment with naloxone methiodide (10 mg /kg, s.c.) had no significant effect on the antitussive effects of either pinacidil or moguisteine. On the other hand, inhaled dihydrocodeine (15-60 μ g / ml) also dose-dependently suppressed the number of capsaicin-induced coughs. The antitussive effect of inhaled dihydrocodeine was significantly antagonized by pretreatment with naloxone methiodide (10 mg /kg, s.c.), but not by glibenclamide (10 mg /kg, i.p.). These results indicate that inhaled pinacidil and moguisteine both attenuate capsaicin-induced coughs. Pinacidil and moguisteine may exert their antitussive effects through the activation of ATP-sensitive K+ channels in the tracheobronchial tract. Furthermore, it is possible that ATP-sensitive K+ channels may be involved in the antitussive effects of peripherally acting non-narcotic antitussive drugs.
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δ-Opioid Receptor Antagonists as a New Concept for Central Acting Antitussive Drugs
Pulmonary pharmacology & therapeutics, 2002Co-Authors: Junzo KameiAbstract:Our recent findings indicated that mu- and kappa-opioid receptors enhance each other's antitussive processes. However, delta-opioid receptors played an inhibitory role in antitussive processes mediated by the mu- and kappa-opioid receptors. We also concluded that delta(1)-opioid receptors may play an inhibitory role, whereas delta(2)-opioid receptors may play a synergistic role, in antitussive processes mediated by mu-opioid receptors. Furthermore, we clearly demonstrated that delta-opioid receptor antagonists, such as naltrindole and 7-benzylidenenaltrexone, produced potent antitussive effects. These delta-opioid receptor-mediated antitussive effects may be mediated by the antagonism of delta(1)-, but not delta(2)-opioid receptors. In this review, we study the possibility of the delta-opioid receptor antagonist as a new concept for central acting antitussive drugs.
Kayo Morita - One of the best experts on this subject based on the ideXlab platform.
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Antitussive effect of WIN 55212-2, a cannabinoid receptor agonist.
European journal of pharmacology, 2003Co-Authors: Kayo Morita, Junzo KameiAbstract:Several lines of evidence indicate that the opioid and cannabinoid systems produce synergistic interactions. The present study examined the opioid receptors involved in the antitussive effect of WIN 55212-2 ((R)-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate), a high-affinity cannabinoid receptor agonist, in mice. WIN 55212-2, at doses of 0.3-3 mg/kg ip, produced a dose-dependent antitussive effect. This antitussive effect of WIN 55212-2 was antagonized by pretreatment with either methysergide (3 mg/kg ip), a 5-HT receptor antagonist, or naloxone (1 mg/kg ip), an opioid receptor antagonist. Furthermore, pretreatment with N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A, 3 mg/kg ip), a cannabinoid CB(1) receptor antagonist, also significantly reduced the antitussive effect of WIN 55212-2. Blockade of mu-opioid receptors by pretreatment with beta-funaltrexamine (40 mg/kg sc) significantly reduced the antitussive effect of WIN 55212-2. However, pretreatment with nor-binaltorphimine (20 mg/kg sc), a kappa-opioid receptor antagonist, did not affect the antitussive effect of WIN 55212-2. Pretreatment with naloxonazine (35 mg/kg sc), a mu(1)-opioid receptor antagonist, also did not affect the antitussive effect of WIN 55212-2. These results indicate that the antitussive effect of WIN 55212-2 is mediated by the activation of cannabinoid CB(1) receptors and mu(2) (naloxonazine-insensitive)-opioid receptors, but not mu(1) (naloxonazine-sensitive)- or kappa-opioid receptors.
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Antitussive effect of WIN 55212-2, a cannabinoid receptor agonist.
European Journal of Pharmacology, 2003Co-Authors: Kayo Morita, Junzo KameiAbstract:Abstract Several lines of evidence indicate that the opioid and cannabinoid systems produce synergistic interactions. The present study examined the opioid receptors involved in the antitussive effect of WIN 55212-2 (( R )-(+)-[2,3-dihydro-5-methyl-3-[4-morpholinylmethyl]-pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl) methanone mesylate), a high-affinity cannabinoid receptor agonist, in mice. WIN 55212-2, at doses of 0.3–3 mg/kg ip, produced a dose-dependent antitussive effect. This antitussive effect of WIN 55212-2 was antagonized by pretreatment with either methysergide (3 mg/kg ip), a 5-HT receptor antagonist, or naloxone (1 mg/kg ip), an opioid receptor antagonist. Furthermore, pretreatment with N -(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H -pyrazole-3-carboxamide hydrochloride (SR141716A, 3 mg/kg ip), a cannabinoid CB 1 receptor antagonist, also significantly reduced the antitussive effect of WIN 55212-2. Blockade of μ-opioid receptors by pretreatment with β-funaltrexamine (40 mg/kg sc) significantly reduced the antitussive effect of WIN 55212-2. However, pretreatment with nor-binaltorphimine (20 mg/kg sc), a κ-opioid receptor antagonist, did not affect the antitussive effect of WIN 55212-2. Pretreatment with naloxonazine (35 mg/kg sc), a μ 1 -opioid receptor antagonist, also did not affect the antitussive effect of WIN 55212-2. These results indicate that the antitussive effect of WIN 55212-2 is mediated by the activation of cannabinoid CB 1 receptors and μ 2 (naloxonazine-insensitive)-opioid receptors, but not μ 1 (naloxonazine-sensitive)- or κ-opioid receptors.
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Inhaled pinacidil, an ATP-sensitive K+ channel opener, and moguisteine have potent antitussive effects in guinea pigs.
Japanese Journal of Pharmacology, 2002Co-Authors: Kayo Morita, Kenji Onodera, Junzo KameiAbstract:Abstract We investigated whether inhaled pinacidil and moguisteine inhibit capsaicin-induced coughs in guinea pigs. Inhaled pinacidil (15-60 μ g / ml), an ATP-sensitive K+ channel opener, and moguisteine (15-60 μ g / ml) each dose-dependently inhibited the number of capsaicin-induced coughs. The antitussive effects of pinacidil and moguisteine were significantly antagonized by pretreatment with glibenclamide (10 mg /kg, i.p.), an ATP-sensitive K+ channel blocker. However, pretreatment with naloxone methiodide (10 mg /kg, s.c.) had no significant effect on the antitussive effects of either pinacidil or moguisteine. On the other hand, inhaled dihydrocodeine (15-60 μ g / ml) also dose-dependently suppressed the number of capsaicin-induced coughs. The antitussive effect of inhaled dihydrocodeine was significantly antagonized by pretreatment with naloxone methiodide (10 mg /kg, s.c.), but not by glibenclamide (10 mg /kg, i.p.). These results indicate that inhaled pinacidil and moguisteine both attenuate capsaicin-induced coughs. Pinacidil and moguisteine may exert their antitussive effects through the activation of ATP-sensitive K+ channels in the tracheobronchial tract. Furthermore, it is possible that ATP-sensitive K+ channels may be involved in the antitussive effects of peripherally acting non-narcotic antitussive drugs.
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Antagonistic effect of buprenorphine on the antitussive effect of morphine is mediated via the activation of μ1-opioid receptors
Life Sciences, 1995Co-Authors: Junzo Kamei, Kayo Morita, Akiyoshi Saitoh, H NagaseAbstract:Abstract The effect of buprenorphine on the antitussive effect of morphine was examined in mice. Buprenorphine at doses of 0.1,0.3 and 1 mg/kg given i.p. alone have no effects on the % inhibition in the number of capsaicin-induced coughs. However, pretreatment with the same doses of buprenorphine for 2 hr significantly attenuated the antitussive effect of morphine (3 mg/Kg, I.p.). Naloxonazine, a selective μ1-opioid receptor antagonist, had no effect on the antitussive effect of morphine, but blocks the antagonistic effect of buprenorphine on antitussive effect of morphine. These results suggest that buprenorphine antagonizes the antitussive effect of morphine via the activation of μ1-opioid receptors.
Kazuo Takahama - One of the best experts on this subject based on the ideXlab platform.
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Centrally acting non-narcotic Antitussives prevent hyperactivity in mice: Involvement of GIRK channels.
Pharmacology biochemistry and behavior, 2016Co-Authors: Fumio Soeda, Tetsuya Shirasaki, Yoshiko Fujieda, Mizue Kinoshita, Kazuo TakahamaAbstract:We have previously reported that centrally acting non-narcotic Antitussives inhibited G protein-coupled inwardly rectifying potassium (GIRK) channel-activated currents, and that the Antitussives had multiple pharmacological actions on various models of intractable brain diseases in rodents. In this study, the question of whether these Antitussives inhibit drug-induced hyperactivity in mice was investigated. Antitussives, such as cloperastine and tipepidine, at cough suppressant doses, inhibited an increase in ambulation of mice neonatally treated with 6-hydroxydopamine. In addition, all Antitussives studied inhibited an increase in methamphetamine-induced hyperactivity in mice. Methylphenidate, which is used for treatment of ADHD, inhibited 6-hydroxydopamine-lesion-induced, but not methamphetamine-induced, hyperactivity in mice. By the rota-rod test, the drugs had little effect on motor coordination of the hyperactive mice. Significant correlation was found between the ameliorating effects of Antitussives on methamphetamine-induced hyperactivity and their inhibitory actions on GIRK channel currents (coefficient factor, 0.998). Furthermore, tertiapin, a GIRK channel blocker, prevented an increase in methamphetamine-induced hyperactivity of mice. These results demonstrated that antitussive drugs (cloperastine, tipepidine and caramiphen) possessing inhibitory action on GIRK channels inhibit drug-induced hyperactivity in mice, suggesting that such Antitussives may potentially be therapeutic for patients with ADHD.
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multiple pharmacological actions of centrally acting Antitussives do they target g protein coupled inwardly rectifying k girk channels
Journal of Pharmacological Sciences, 2012Co-Authors: Kazuo TakahamaAbstract:Abstract Antitussive drugs have been used for decades and their modes of action are well elucidated. However, recent studies on the mechanism of their antitussive action seem to be opening a new way for discovery or development of novel drugs for intractable brain diseases including psychiatric disorders. Antitussives inhibit the currents caused by activation of G protein-coupled inwardly rectifying K+ (GIRK) channels in neurons. In our own studies carried out so far, we found that Antitussives possessing an inhibitory action on GIRK channels, similar to the effects of an enriched environment, ameliorate symptoms of intractable brain diseases in various animal models. In this review, the multiple pharmacological actions of the Antitussives are described, and their mechanisms are discussed addressing GIRK channels as a possible molecular target.
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A novel antidepressant-like action of drugs possessing GIRK channel blocking action in rats
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2010Co-Authors: Kazuaki Kawaura, Fumio Soeda, Tetsuya Shirasaki, Sokichi Honda, Kazuo TakahamaAbstract:We have previously found that antitussive drugs inhibit G protein-coupled inwardly rectifying potassium (GIRK) channel currents in brain neurons. Potassium efflux through GIRK channels causes membrane hyperpolarization, and thus plays an important role in the inhibitory regulation of neuronal excitability. Because GIRK channels are coupled to various G protein-coupled receptors including monoamine receptors, Antitussives are possible to affect the levels of various neurotransmitters in the brain. Many currently available antidepressants have been developed based on the monoamine theory for the etiology of depression. We hypothesized that new drugs such as tipepidine may lead to changes in the balance of monoamine levels in the brain resulting in improvement in symptoms of depression. Therefore, we investigated whether or not the drugs have antidepressant activity in the animal models. Male Wistar rats (200-240 g) were used. Tipepidine, cloperastine and caramiphen significantly reduced the immobility in forced swimming test (FST) using normal rats. All drugs had little effect on loco-motor activity. The effects on the forced swimming were inhibited by treatment with AMPT, but not PCPA. Tipepidine also inhibited hyperactivity in olfactory bulbectomized rats. Interestingly, tipepidine also significantly reduced the immobility in FST using ACTH-treated rats which is a model of depression resistant to treatment with antidepressants. Given these results together with cumulated findings, it is suggested that tipepidine may have a novel antidepressant-like action, and that the effect may be caused at least partly through the action on the catecholaminergic system in the brain.
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Ameliorating effects of cloperastine on dysfunction of the urinary bladder caused by cerebral infarction in conscious rats
Canadian Journal of Physiology and Pharmacology, 2009Co-Authors: Yamamotog. Yamamoto, Fumio Soeda, Tetsuya Shirasaki, Kazuo TakahamaAbstract:We investigated the effects of the centrally acting Antitussives dextromethorphan and cloperastine on urinary bladder dysfunction 24 h after cerebral infarction in rats using the cystometry technique. First, cystometrography was performed in conscious male Sprague–Dawley rats. Cerebral infarction was then induced by occlusion of the left middle cerebral artery. Twenty-four hours after cerebral infarction, the effect of each drug on micturition disorder was estimated for 5 parameters: bladder capacity, maximum voiding pressure, micturition latency, flow rate, and urethral resistance. Cerebral infarction markedly reduced bladder capacity, micturition latency, and flow rate and increased urethral resistance. After cerebral infarction, intravenous dosing of saline had no effect on these parameters. Dextromethorphan (20 mg/kg) and cloperastine (2.5 and 5.0 mg/kg) at antitussive effective doses significantly increased bladder capacity and micturition latency. Unlike dextromethorphan, cloperastine ameliorated de...
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Central and peripheral mechanisms of narcotic Antitussives: codeine-sensitive and -resistant coughs
Cough, 2007Co-Authors: Kazuo Takahama, Tetsuya ShirasakiAbstract:Narcotic Antitussives such as codeine reveal the antitussive effect primarily via the μ-opioid receptor in the central nervous system (CNS). The κ-opioid receptor also seems to contribute partly to the production of the antitussive effect of the drugs. There is controversy as to whether δ-receptors are involved in promoting an antitussive effect. Peripheral opioid receptors seem to have certain limited roles. Although narcotic Antitussives are the most potent Antitussives at present, certain types of coughs, such as chronic cough, are particularly difficult to suppress even with codeine. In guinea pigs, coughs elicited by mechanical stimulation of the bifurcation of the trachea were not able to be suppressed by codeine. In gupigs with sub-acute bronchitis caused by SO_2 gas exposure, coughing is difficult to inhibit with centrally acting Antitussives such as codeine. Some studies suggest that neurokinins are involved in the development of codeine-resistant coughs. However, evidence supporting this claim is still insufficient. It is very important to characterize opiate-resistant coughs in experimental animals, and to determine which experimentally induced coughs correspond to which types of cough in humans. In this review, we describe the mechanisms of antitussive effects of narcotic Antitussives, addressing codeine-sensitive and -resistant coughs, and including our own results.
Lolkje T. W. Jong-van Den Berg - One of the best experts on this subject based on the ideXlab platform.
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The Effects of Antitussive Treatment of ACE Inhibitor-Induced Cough on Therapy Compliance: A Prescription Sequence Symmetry Analysis
Drug Safety, 2013Co-Authors: Stefan Vegter, Pieter Boer, Klaas Willem Dijk, Sipke Visser, Lolkje T. W. Jong-van Den BergAbstract:Background A common adverse effect of angiotensin-converting enzyme inhibitors (ACEI) is a persistent dry cough. Physicians and pharmacists who fail to recognise dry cough to be ACEI related may prescribe Antitussives, instead of recommended ACEI substitution. Objective The aim of this study was to determine the influence of antitussive treatment of ACEI-induced cough on ACEI therapy compliance. Methods Prescription data from community pharmacies between 2000 and 2012 were retrieved from the IADB.nl database (InterAction Database) in The Netherlands. A prescription sequence symmetry analysis was used to determine whether antitussive agents were prescribed more often following ACEI initiation (cases) than the other way around (controls). ACEI therapy compliance was assessed using the proportion of days covered (PDC) method; patients with a PDC of at least 80 % were considered compliant. Compliance was compared between patients receiving Antitussives for ACEI-induced cough and patients receiving Antitussives for other reasons and patients who did not receive Antitussives. Results A total of 1,898 starters of ACEI and Antitussives within a half-year time span were included. A significant excess of patients received Antitussives after ACEI initiation compared with before ACEI initiation (1,269 cases vs. 629 controls), yielding a sequence ratio of 2.0 (95 % CI 1.8–2.2). The estimated proportion of patients with ACEI-induced cough receiving Antitussives decreased over time: from 20.4 % in 2000–2004 to 8.0 % in 2008–2012. ACEI therapy compliance in patients receiving Antitussives due to ACEI initiation was 52.4 %, significantly lower than compliance in control patients receiving Antitussives for cough unrelated to ACEI (75.5 %, P
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Artsen en apothekers miskennen vaak een door ACE-remmers geïnduceerde prikkelhoest, wat de therapietrouw verlaagt
Pharmaceutisch weekblad, 2012Co-Authors: Stefan Vegter, Pieter T. De Boer, Klaas Willem Van Dijk, Sipke T. Visser, Lolkje T. W. Jong-van Den BergAbstract:OBJECTIVE: A common side-effect of angiotensin-converting enzyme inhibitors (ACEi) is a persistent dry cough. Physicians and pharmacists who fail to recognise a dry cough to be ACEi-related may attempt to treat it with Antitussives, instead of recommended ACEi substitution. The aim of this study was to quantify such prescription behaviour, as well as its influence on therapy compliance. DESIGN AND METHODS: Drug dispensing data were retrieved from the IADB.nl database in The Netherlands. A prescription sequence symmetry analysis was used to determine whether antitussive agents were prescribed more often following ACEi initiation than the other way around. Therapy compliance in both groups was assessed using the proportion of days covered (PDC) method; patients with a PDC ≥ 80% were considered compliant. RESULTS: 1601 patients were incident users of both ACEi and Antitussives within a half-year time span. There was a significant excess of patients prescribed antitussive agents after ACEi initiation (1075 versus 526), yielding a sequence ratio of 2.0 (95% confidence interval 1.8-2.3). Therapy compliance in patients receiving Antitussives after ACEi initiation was 58%, significantly lower than therapy compliance in control patients, which was 77% (P
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Misdiagnosis and mistreatment of a common side-effect - angiotensin-converting enzyme inhibitor-induced cough
British journal of clinical pharmacology, 2010Co-Authors: Stefan Vegter, Lolkje T. W. Jong-van Den BergAbstract:AIMS Angiotensin-converting enzyme inhibitors (ACEi) are frequently prescribed for various cardiovascular and renal diseases. A common side-effect of these drugs is a persistent dry cough. Physicians who fail to recognize a dry cough to be ACEi-related may attempt to treat it with antitussive agents instead of recommended ACEi substitution. Prescription behaviour in the general population considering treatment of the side-effect with antitussive agents has not been studied before. METHODS Drug dispensing data between 2000 and 2007 were retrieved from the IADB.nl database. A prescription sequence symmetry analysis was used to determine whether antitussive agents were prescribed more often following ACEi initiation than the other way around. A logistic regression model was fitted to determine predictors. RESULTS We identified 27 446 incident users of ACEi therapy. One thousand and fifty-four patients were incident users of both ACEi and Antitussives within a half-year time span. There was an excess of patients being prescribed antitussive agents after ACEi initiation (703 vs. 351), adjusted sequence ratio 2.2 [confidence interval (CI) 1.9, 2.4]. Female patients were more likely to be prescribed antitussive agents following ACEi therapy initiation, odds ratio 1.4 (CI 1.1, 1.9), age and co-medications were not significant predictors. CONCLUSIONS There was a significant and clinically relevant excess of patients receiving Antitussives after ACEi initiation. The results suggest that cough as a side-effect of ACEi is not recognized as being ACEi-related or is symptomatically treated with antitussive agents instead of ACEi substitution. The estimated frequency of antitussive treatment of ACEi-induced dry cough is 15%.
Y. Kasuya - One of the best experts on this subject based on the ideXlab platform.
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Antitussive effect of dihydroetorphine in mice.
European journal of pharmacology, 1994Co-Authors: Junzo Kamei, Yuriko Iwamoto, M Misawa, H Nagase, T Suzuki, Y. KasuyaAbstract:Abstract The present study examined the opioid receptors involved in the antitussive effect of dihydroetorphine in mice. Dihydroetorphine suppressed coughs dose dependently at doses between 0.1–1 μg/kg i.p. Blockade of μ-opioid receptors by pretreatment with β-funaltrexamine significantly reduced the antitussive effect of dihydroetorphine. Furthermore, the antitussive effect of dihydroetorphine was also antagonized by nor-binaltorphimine, a κ-opioid receptor antagonist. However, pretreatment with naltrindole, a δ-opioid receptor antagonist, did not affect the antitussive effect of dihydroetorphine. These results indicate that the antitussive effect of dihydroetorphine is mediated by the activation of μ-opioid receptors and κ-opioid receptors, but not δ-opioid receptors.
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Involvement of δ1-opioid receptor antagonism in the antitussive effect of δ-opioid receptor antagonists
European Journal of Pharmacology, 1994Co-Authors: Junzo Kamei, Yuriko Iwamoto, M Misawa, H Nagase, T Suzuki, Y. KasuyaAbstract:Abstract The effects of 7-benzylidenenaltrexone(BNTX), a selective δ 1 -opioid receptor antagonist, and naltriben, a selective δ 2 -opioid receptor antagonist, on the capsaicin-induced cough reflex were studied in mice. I.p. administration of BNTX in doses from 0.1 to 3.0 mg/kg reduced the number of coughs dose dependently. The antitussive effect of BNTX was antagonized by [ D -Pen 2,5 ]enkephalin (DPDPE), a selective δ 1 -opioid receptor agonist, while [ D -Ala 2 ]deltorphin II, a selective δ 2 -opioid receptor agonist, had no effect on the antitussive effect of BNTX. Pretreatment with nor-binoltorphimine, a selective κ-opioid receptor antagonist, had no significant effect on the antitussive effect of BNTX. I.p. administration of naltriben, in doses of 1 and 3 mg/kg, also significantly decreased the number of coughs. Although the antitussive effect of naltriben was antagonized by nor-binaltorphimine, the antitussive effect of naltriben was not attenuated by either DPDPE or [ D -Ala 2 ]deltorphin II. The antitussive effects of neither BNTX nor naltriben were antagonized by β-funaltrexamine, a selective μ-opioid receptor antagonist. Thus, it seems likelythat the δ 1 -opioid receptor antagonism may be involved in the antitussive effect of δ-opioid receptor antagonists.
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Antitussive effect of (+/-) pentazocine in diabetic mice is mediated by delta-sites, but not by mu- or kappa-opioid receptors.
Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology, 1994Co-Authors: Junzo Kamei, Yuriko Iwamoto, M Misawa, H Nagase, Y. KasuyaAbstract:The effects of streptozotocin-induced diabetes on the antitussive effect of (+/-) pentazocine were examined in mice. Intracerebroventricular (i.c.v.) administration of (+/-) pentazocine produced a dose-dependent antitussive effect in both diabetic and non-diabetic mice. There were no significant differences in the antitussive effect of (+/-) pentazocine in diabetic and non-diabetic mice. The antitussive effect of i.c.v. (+/-) pentazocine was partially, but significantly, reduced in non-diabetic mice following pretreatment with either beta-funaltrexamine, a selective mu-opioid antagonist, or rimcazole, a specific sigma-site antagonist. The antitussive effect of (+/-) pentazocine in diabetic mice was significantly antagonized by pretreatment with rimcazole. However, beta-funaltrexamine had no effect on the antitussive effect of (+/-) pentazocine in diabetic mice. Furthermore, nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of (+/-) pentazocine in either non-diabetic or diabetic mice. These results suggest that although the antitussive effect of i.c.v. (+/-) pentazocine in non-diabetic mice is mediated by both mu-opioid receptors and sigma-sites, in diabetic mice this effect is mainly mediated by sigma-sites.
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Antitussive effects of naltrindole, a selective δ-opioid receptor antagonist, in mice and rats
European Journal of Pharmacology, 1993Co-Authors: Junzo Kamei, Yuriko Iwamoto, M Misawa, H Nagase, T Suzuki, Y. KasuyaAbstract:Abstract The effects of naltrindole, a selective δ-opioid receptor antagonist, on the capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal administration of naltrindole decreased the number of coughs both in mice and rats dose dependently. The cough-depressant effects reached a peak 15 min after the administration of naltrindole and lasted more than 120 min. Pretreatment with [ D -Pen 2 , D -Pen 5 ]enkephalin, a selective δ-opioid receptor agonist, partially but significantly reduced the antitussive effect of naltrindole. Blockade of ϰ-opioid receptors by pretreatment with nor-binaltorphimine also partially antagonized the antitussive effect of naltrindole. However, the antitussive effect of naltrindole was not antagonized by β-funaltrexamine, a selective μ-opioid receptor antagonist. Thus, it is possible that the antitussive effect of naltrindole may be mediated, in part, by ϰ-opioid receptors. The present results provide evidence for the development of δ-opioid antagonists, especially naltrindole, for use as antitussive drugs.
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Antitussive effect of β-endorphin is mediated by μ-opioid receptors, but not by κ- or ε-opioid receptors
European Journal of Pharmacology, 1993Co-Authors: Junzo Kamei, Yuriko Iwamoto, M Misawa, H Nagase, Y. KasuyaAbstract:The present study examined the opioid receptors involved in the antitussive effect of β-endorphin in mice. β-Endorphin injected i.c.v. depresses coughs dose dependently in doses from 0.1 to 1 μg. Blockade of μ-opioid receptors by pretreatment with β-funaltrexamine significantly reduced the antitussive potency of i.c.v. β-endorphin. However, the antitussive effect of β-endorphin was not antagonized by nor-binaltorphimine, a κ-opioid receptor antagonist. Moreover, i.c.v. injection of β-endorphin-(1-27), an E-opioid receptor antagonist, did not affect the antitussive effect of β-endorphin