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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The general pharmacology of buprenorphine, a potent analgesic agent derived from oripavine, is described. 2. After cute administration of buprenorphine, the spontaneous locomotor activity of mice was increased; rats displayed stereotyped licking and biting movements; behavioural depression was marked in guinea-pigs but mild in rhesus monkeys. The behaviour of cats was unchanged. 3. In general, buprenorphine reduced heart rate but had no significant effect on arterial blood pressure in conscious rats and dogs. 4. In anaesthetized, open-chest cats buprenorphine (0.10 and 1.0 mg/kg, i.v.) caused no major haemodynamic changes. 5. Buprenorphine (0.01-10 mg/kg i.a.) and morphine (0.30-30 mg/kg, i.a.) increased arterial PCO2 values and reduced PO2 values in conscious rats. With doses of buprenorphine greater than 0.10 mg/kg (a) the duration of respiratory depression became less, (b) ceiling effects occurred such that the maximum effects produced were less than those obtained with morphine. 6. Buprenorphine was a potent and long-lasting antagonist of citric acid-induced coughing in guinea-pigs. 7. At a dose level 20 times greater than the ED50 for antinociception (tail pressure), morphine suppressed urine output to a greater extent than the corresponding dose of buprenorphine in rats. 8. Over the range 0.01-1.0 mg/kg (s.c.), buprenorphine slowed the passage of a charcoal meal along the gastrointestinal tract in rats. After doses in excess of 1 mg/kg, the meal travelled increasingly further such that the distances measured at 10 and 30 mg/kg did not differ significantly from control values. In contrast, the morphine dose-response relationship was linear.
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PMID:The animal pharmacology of buprenorphine, an oripavine analgesic agent. 40 49

1. Protection by codeine 20 mg, dextromethorphan 30 mg, noscapine 30 mg, and placebo against citric acid-induced cough was determined in eighteen healthy subjects. 2. Drug differences occurred at 2 1/2 h following ingestion of the drugs but not at 1 1/4 h. 3. Only coideine 20 mg had a greater antitussive action than placebo, but dextromethorphan 30 mg also did not differ from codeine 20 mg. 4. This technique may offer a useful screening test for the activity of new potential antitussive compounds in man.
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PMID:Comparison of the antitussive effects of codeine phosphate 20 mg, dextromethorphan 30 mg and noscapine 30 mg using citric acid-induced cough in normal subjects. 52 35

Inhalation of histamine diphosphate aerosol (1.6 per cent, 10 breaths) produced a 218 +/- 54.6 per cent (mean +/- SE) increase in airway resistance in 16 normal subjects with colds compared with a 30.5 +/- 5.5 per cent increase in 11 healthy control subjects (P less than 0.01). There was no significant difference in mean baseline airway resistance between the two groups. Inhalation of saline produced no significant change in airway resistance in either group. Isoproterenol hydrochloride (0.5 per cent, 1 breath) or atropine sulfate aerosol (0.2 per cent, 20 breaths) each reversed and prevented the increase in airway resistance by histamine, indicating that the bronchoconstriction was caused by smooth muscle contraction and that post-ganglionic, cholinergic pathways were involved in the mechanism. In 6 subjects with colds, citric acid aerosol (10 per cent, 5 breaths) caused bronchoconstriction that lasted up to 30 sec after inhalation, a significantly greater effect than that observed in control subjects or in the same subjects after recovery (P less than 0.05). Prior inhalation of atropine aerosol (0.2 per cent, 20 breaths) prevented the bronchoconstriction after citric acid aerosol in all 6 subjects. The threshold concentration of citric acid that produced cough in 7 subjects with colds was significantly lower than that in control subjects or in the 7 subjects after recovery (P less than 0.05), suggesting that the exaggerated cholinergic response was due to a decreased threshold for stimulation of the rapidly adapting sensory receptors in the airways. We have provided evidence that respiratory viral infections that produce airway epithelial damage temporarily cause these subjects to develop more bronchoconstriction after inhaling smaller doses of histamine than do healthy subjects. The fact that atropine prevents this response and that the threshold to cough is temporarily decreased is compatible with our hypothesis that airway epithelial damage by infection exposes and, thus, "sensitizes" the rapidly adapting airway receptors to inhaled irritants, causing increased bronchoconstriction via a vagal reflex. Damage to the airway epithelium may occur as a result of mechanical factors, inhaled chemicals, and pollutants, such as ozone, infections, or perhaps as a result of the action of materials released endogenously (e.g., from mast cells, white blood cells, or platelets). "Sensitization" of rapidly adapting sensory receptors in the airways may be an important factor in asthma and in other diseases of airways.
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PMID:Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. 124 26

1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering-Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering-Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The Ve/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min.
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PMID:The effect of anaesthesia of the airway in dog and man: a study of respiratory reflexes, sensations and lung mechanics. 127 53

Levodropropizine is the levo-rotatory (S)-enantiomer of dropropizine, a racemic non-opiate antitussive agent which has been used clinically for many years. Compared with the racemic drug, levodropropizine exhibits in animal models similar antitussive activity but considerably lower central nervous system (CNS) depressant effects. It is also less likely to cause sedation in treated patients. Since the comparative antitussive potency of the two drugs in clinical experimental models has not been evaluated, the authors performed a randomized, double blind, cross over investigation in which the effects of single oral doses (60 and 90 mg) of levodropropizine and dropropizine were assessed by using the citric acid-induced cough model in eight normal volunteers. Stimulation tests involved inhalation of individual cumulative doses of citric acid (6.3 to 53.3 mg) which at pre-study assessment had been found to induce reproducibly at least ten coughs over a 30 sec period. Each subject was studied by repeating the citric acid stimulation test four times (0 h, 1 h, 2 h and 6 h) on each of five different days separated by intervals of at least three days. In the absence of drug administration (control session), cough response to citric inhalation was remarkably reproducible throughout the 6 h period of observation. A marked and statistically significant reduction in cough response (to about one third--one sixth of the pre-drug values) was observed 1 h after intake for both compounds. At subsequent testing 2 h and 6 h after dosing, cough response was still depressed and did not differ significantly from that observed at 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative study of the antitussive activity of levodropropizine and dropropizine in the citric acid-induced cough model in normal subjects. 129 24

The effects of alpha 2-adrenoceptor and GABA receptor agonists on citric acid-induced cough and increased tidal volume were investigated in conscious guinea pigs. Inhalation of low doses of B-HT 920 (5-allyl-2-amino 5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride), and xylazine significantly inhibited citric acid-induced cough and tidal volume increases. Intraperitoneal administration of higher doses of B-HT 920 than those given by aerosol were ineffective. The inhibitory effects of B-HT 920 were antagonised by prior intraperitoneal administration of yohimbine, but not atropine. Inhalation of GABA or baclofen inhibited tidal volume increases, but had no effect on cough. Inhaled alpha 2-adrenoceptor or GABA agonists had no effect on the reduced respiratory rate after citric acid inhalation. It is concluded that alpha 2-adrenoceptor agonists inhibit cough via a mechanism which may not be related to their ability to reduce citric acid-induced tidal volume increases, since GABA and baclofen inhibited tidal volume increases but not cough. We suggest that alpha 2-adrenoceptor agonists may have therapeutic potential in the treatment of cough.
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PMID:Effects of inhaled alpha 2-adrenoceptor and GABAB receptor agonists on citric acid-induced cough and tidal volume changes in guinea pigs. 135 50

Prostaglandins have been shown to influence the sensitivity of the cough reflex. To investigate putative mechanisms of this, we examined the effects of inhaled prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) on human cough responses elicited by two challenges, low chloride solution and capsaicin, which may activate different neural pathways. Baseline cough challenges were followed after 2 h by five breaths of PGE2, PGF2 alpha, or citric acid as a control. Cough challenges were repeated after 1 min. Potentiation of capsaicin responses occurred after PGE2 (median increase 2 coughs/min, range 0-7, P less than 0.01) and PGF2 alpha (median increase 8 coughs/min, range -3 to 27, P less than 0.01) compared with control. The effect of PGF2 alpha was greater (P less than 0.05) than that of PGE2. Potentiation of low chloride responses also occurred after PGF2 alpha (median increase 7 coughs/2 min, range -1 to 19, P less than 0.01), but effects of PGE2 were insignificant against this challenge (median change -1 coughs/2 min, range -4 to 13). These data suggest that PGE2 and PGF2 alpha have different effects on the sensitivity of the human cough reflex, which may be relevant during airway disease.
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PMID:Contrasting effects of prostaglandins E2 and F2 alpha on sensitivity of the human cough reflex. 139 93

The relationship between airway responsiveness to bronchoconstrictor- and cough-inducing stimuli has been examined in Ascaris suum-sensitized conscious guinea-pigs. Guinea-pigs were sensitized to Ascaris suum [4000 PNU and 100 mg Al(OH)3 i.p. on days 1 and 7] and then challenged with aerosolized antigen on days 21, 28 and 35. At day 35, antigen-exposure produced an early bronchoconstrictor response (EBR) and in about 50% of the animals also a late bronchoconstrictor response (LBR) commencing 4-8 h later. The bronchial responsiveness to inhaled histamine was increased in sensitized guinea-pigs and increased further 20-24 h after acute antigen challenge. Guinea-pigs developing only EBR were equally sensitive to histamine as those having both EBR and LBR. In contrast, the cough and reflex bronchoconstriction produced by inhaled citric acid (0.40 M, acting on capsaicin-sensitive sensory neurons) and cigarette smoke (3 min exposure; exciting both capsaicin-sensitive neurons and rapidly adapting stretch receptors) were not altered by sensitization. Furthermore, acute antigen challenge did not alter the effect of citric acid as measured 24 h later. The antigen-induced airway hyperresponsiveness to histamine was not accompanied by an altered sensitivity of airway sensory nerves mediating cough (and reflex bronchoconstriction), demonstrating that bronchial- (airway obstruction) and sensory- (cough) hyperresponsiveness involve separate and independent mechanisms.
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PMID:Relationship of airway responsiveness to agents causing bronchoconstriction and cough in sensitized guinea-pigs. 144 41

We have evaluated the properties of capsaicin as a selective cough-inducing agent in healthy human subjects. Despite frequent coughing, the subjects could inhale repeated breaths of capsaicin aerosol during 60 s without difficulty. Cough started immediately on inhalation and was most intense during the first 30 s. Cough always disappeared promptly when the capsaicin inhalation was terminated. The cough response was well reproducible and concentration-dependent up to 10 microM; at higher concentrations there was a distinct plateau of the cough response. Specific airway conductance was not changed 3 min after 50 microM capsaicin. Capsaicin (> or = 10 microM) had a burning taste, but there were no visual signs of pharyngitis or laryngitis. Citric acid (nebulized solutions 0.125 to 32%) had a choking effect and could be administered only as single breaths. There was no correlation between the cough response to citric acid and to capsaicin. Inhaled lidocaine (20 and 80 mg from nebulized solutions) caused a dose-dependent inhibition of capsaicin-induced cough. Lidocaine suppressed citric acid-induced cough as effectively as capsaicin-induced cough. In conclusion, we have characterized capsaicin-induced cough and demonstrated that it can be a useful tool in the study of cough reactivity and for evaluation of antitussive agents in humans. Capsaicin may be complementary to citric acid and may offer experimental advantages over this traditional tussive stimulus.
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PMID:Capsaicin-induced cough in humans. 148 23

Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adaptation of cough reflex with different types of stimulation. 148 81


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