Showing papers on "Antitussive Agent published in 2009"

In vivo antitussive activity of Coccinia grandis against irritant aerosol and sulfur dioxide-induced cough model in rodents

Abstract: Coccinia grandis ( Cucurbitaceae ) has extensi v ely used to get relief from asthma and cough by the indigenous people of India. T he antitussive effect of aerosols of two different concentrations (2.5%, 5%w/v) of methanol extract of C. grandis fruits were tested by counting the numbers of coughs produced due to aerosols of citric acid, 10 min after exposing the male guinea pigs to aerosols of test solutions for 7 min. In another set of experiment methanol extract was investigated for its therapeutic efficacy on a cough model induced by sulfur dioxide gas in mice. The results showed significant reduction of cough number obtained in the presence of both concentrations of methanol extract as that of the prototype antitussive agent codeine phosphate. Also, methanol extract exhibited significant antitussive effect at 100, 200 and 400 mg/kg, per orally by inhibiting the cough by 20.57, 33.73 and 56.71% within 90 min of performing the experiment.

Central mechanisms II: pharmacology of brainstem pathways.

Abstract: Following systemic administration, centrally acting antitussive drugs are generally assumed to act in the brainstem to inhibit cough. However, recent work in humans has raised the possibility of suprapontine sites of action for cough suppressants. For drugs that may act in the brainstem, the specific locations, types of neurones affected, and receptor specificities of the compounds represent important issues regarding their cough-suppressant actions. Two medullary areas that have received the most attention regarding the actions of antitussive drugs are the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral respiratory column. Studies that have implicated these two medullary areas have employed both microinjection and in vitro recording methods to control the location of action of the antitussive drugs. Other brainstem regions contain neurones that participate in the production of cough and could represent potential sites of action of antitussive drugs. These regions include the raphe nuclei, pontine nuclei, and rostral ventrolateral medulla. Specific receptor subtypes have been associated with the suppression of cough at central sites, including 5-HT1A, opioid (μ, κ, and δ), GABA-B, tachykinin neurokinin-1 (NK-1) and neurokinin-2, non-opioid (NOP-1), cannabi-noid, dopaminergic, and sigma receptors. Aside from tachykinin NK-1 receptors in the NTS, relatively little is known regarding the receptor specificity of putative antitussive drugs in particular brainstem regions. Our understanding of the mechanisms of action of antitussive drugs would be significantly advanced by further work in this area.

Peripheral mechanisms II: the pharmacology of peripherally active antitussive drugs.

Abstract: Cough is an indispensable defensive reflex. Although generally beneficial, it is also a common symptom of diseases such as asthma, chronic obstructive pulmonary disease, upper respiratory tract infections, idiopathic pulmonary fibrosis and lung cancer. Cough remains a major unmet medical need and although the centrally acting opioids have remained the antitussive of choice for decades, they have many unwanted side effects. However, new research into the behaviour of airway sensory nerves has provided greater insight into the mechanisms of cough and new avenues for the discovery of novel non-opioid antitussive drugs. In this review, the pathophysiological mechanisms of cough and the development of novel antitussive drugs are reviewed.

Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor.

Abstract: The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Ver showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver. Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver's central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver's addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver, suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response. These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.

In-vivo Antitussive Activity of Cressa cretica Linn. using Cough Model in Rodents

Abstract: Cressa cretica Linn. Voigt. (Convolulaceae), has also been extensively used to get relief from asthma and cough by the indigenous people of India. In the present study the antitussive effect of the plant was evaluated in two different experimental models. The antitussive effect of aerosols of two different concentrations (2.5%w/v, 5%w/v)of methanolic extract of Cressa cretica Linn. (CME), codeine(0.03g/ml), and normal saline were tested by counting the numbers of coughs produced due to aerosols of citric acid 10 min after exposing the male guinea pigs to aerosols of different solutions (n=6). In another set of experiment CME was investigated for its therapeutic efficacy on a cough model induced by sulfur dioxide gas in mice. The results showed significant reduction of cough number obtained in the presence of both concentrations of CME and codeine. The antitussive effect on guinea pigs of higher concentration of CME was significantly (p<0.01) greater than those of lower concentration and the prototype antitussive agent codeine phosphate (p<0.01). It exhibited significant anti tussive activity as that of codeine phosphate, when compared with control in a dose dependent manner in sulfur dioxide gas induced cough model. The extract at 100, 200 and 400 mg/kg, p.o. showed inhibition of cough by 22.1, 34.35 and 55.44 % within 90 min of performing the experiment.

Central vs. peripheral sites of action of antitussive agents in anesthetized guinea pigs

Abstract: Dextromethorphan (DEX), SKF10047, codeine, DAMGO, mexiletine and baclofen have all been reported to prevent cough, in part, through direct peripheral effects on airway sensory nerves. We evaluated ...

Effects of dextromethorphan on electroconvulsive therapy.

Abstract: 1 Dirks P, Thomas U, Montag D. The cytoplasmic domain of nrCAM binds to PDZ domains of synapse-associated proteins sap90/psd95 and sap97. Eur. J. Neurosci. 2006; 24: 25–31. 2 Hutcheson HB, Olson LM, Bradford Y et al. Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes. BMC Med. Genet. 2004; 5: 12. 3 Sakurai T, Ramoz N, Reichert JG et al. Association analysis of the NrCAM gene in autism and in subsets of families with severe obsessive-compulsive or self-stimulatory behaviors. Psychiatr. Genet. 2006; 16: 251–257. 4 Ishiguro H, Liu QR, Gong JP et al. NrCAM in addiction vulnerability: Positional cloning, drug-regulation, haplotype-specific expression, and altered drug reward in knockout mice. Neuropsychopharmacology 2006; 31: 572–584.