piperidines and rimiterol

The development of beta2-specific sympathomimetic bronchodilators (rimiterol, salbutamol, terbutaline) has made the basic treatment of asthmatic patients more safe and effective. Despite that, the asthmatics should be under careful control and all patients should be taught the correct way to use their bronchodilator aerosols. If a sympathomimetic drug has lost its effectiveness, the patient should be able to have easy contact to the treating physician or outpatient department.

Topics: Adrenergic beta-Agonists; Aerosols; Animals; Asthma; Bronchial Spasm; Bronchodilator Agents; Catechols; Humans; Piperidines

Topics: Absorption; Administration, Oral; Aerosols; Albuterol; Animals; Asthma; Bronchodilator Agents; Catechols; Clinical Trials as Topic; Half-Life; Hemodynamics; Humans; In Vitro Techniques; Injections, Intravenous; Isoproterenol; Kinetics; Muscle Contraction; Myocardial Contraction; Organ Specificity; Piperidines; Terbutaline; Tremor

The potential for rimiterol to protect athletes from exercise-induced asthma (EIA) has not been fully established. Ten athletes with asthma (15 to 30 years of age) undertook 8 minutes of submaximal exercise (80% of anaerobic threshold) on the treadmill ergometer, once after inhaling rimiterol and once after inhaling a placebo. Treatment with all bronchodilator drugs was stopped for the 12 hours preceding each exercise test. Two puffs (400 micrograms) of rimiterol or placebo were administered in a double-blind crossover manner 2 minutes before each exercise test. Lung function measurements were made before exercise and immediately, 5, 10, 15, 20, 25, and 30 minutes after completion of exercise. The results of a two-way analysis of variance revealed significant (p less than 0.01) difference in the FEV1 scores obtained after rimiterol inhalation and placebo inhalation, 5, 10, 15, 20, 25, and 30 minutes after cessation of exercise. After inhalation of rimiterol, there were no significant changes in FEV1. After inhaling the placebo, significant reductions (p less than 0.01) in FEV1 occurred after cessation of exercise (5, 10, 15, and 20 minutes). All subjects exhibited EIA after placebo, and none after rimiterol. The mean maximum drop after exercise in FEV1 after inhalation of rimiterol (2.807 +/- 5.55) and placebo (24.54 +/- 8.4) was significantly different (t = 6.849). It was concluded that inhalation of rimiterol 2 minutes before exercise afforded significant protection from EIA in all subjects tested.

Topics: Administration, Inhalation; Adolescent; Adult; Asthma; Asthma, Exercise-Induced; Catechols; Double-Blind Method; Exercise Test; Female; Forced Expiratory Volume; Humans; Male; Piperidines; Sports

Twenty chronic asthmatics who completed a double-blind cross-over study comparing sustained release aminophylline tablets with placebo had a significant improvement in airways obstruction. Inhaled rimiterol and the aminophylline tablets were shown to act in an additive manner. There was a significant reduction in asthmatic symptoms on active tablets. A further nine patients had to be withdrawn from the study because of adverse side effects.

Topics: Adolescent; Adult; Aerosols; Aged; Aminophylline; Asthma; Catechols; Delayed-Action Preparations; Double-Blind Method; Drug Interactions; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Piperidines; Placebos

1 The effect of i.v. rimiterol was compared with aerosol rimiterol in twelve asthmatic patients. 2 A cumulative dose of rimiterol (1050 microgram) given in six separate injections over 90 min resulted in a mean increase in peak expiratory flow rate (PEFR) of 50.6% and FEV1 of 53.7%. 3 Comparison of the degree of bronchodilation to the same dose of rimiterol administered intravenously or by aerosol, suggested that on average the potency ratio was 10:1, i.e. ten times the aerosol dose was required to produce the equivalent bronchodilator effect. 4 Palpitations, tremor and postural hypotension were common during the first minute after the drug was injected intravenously, but did not occur after aerosol administration. 5 It is suggested that rimiterol by intravenous injection is a useful addition to the treatment of acute asthma.

Topics: Adult; Aged; Asthma; Blood Pressure; Catechols; Female; Forced Expiratory Volume; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Piperidines; Vital Capacity

The metabolic and cardiovascular side-effects of intravenous infusions of therapeutic doses of beta 2-adrenoceptor agonists salbutamol and rimiterol have been determined in four healthy male subjects. There were dose-related increases in plasma glucose, renin activity, serum insulin and heart rate, and significant hyperlactataemia and ketonaemia. There were dose-related decreases in plasma potassium, phosphate and corticosteroids and significant hypocalcaemia and hypomagnesaemia. The effects of equivalent molar amounts of salbutamol and rimiterol were similar. Whichever drug is used, special care is required with patients who may have abnormal glucose tolerance, potassium depletion, or be predisposed to lactic acidosis. Rimiterol may be preferable for infusion because of its short plasma half-life.

Topics: Albuterol; Blood Glucose; Cardiovascular System; Catechols; Half-Life; Humans; Infusions, Parenteral; Insulin; Male; Metabolism; Piperidines; Pulse

Topics: Adult; Aerosols; Aged; Airway Obstruction; Airway Resistance; Catechols; Clinical Trials as Topic; Ethanolamines; Female; Fenoterol; Humans; Male; Middle Aged; Piperidines; Placebos; Time Factors

The onset of action of three sympathomimetic drugs (rimiterol 0.2 mg, terbutaline 0.25 mg and isoprenaline 0.08 mg) administered by metered dose inhaler was compared in 12 asthmatics. In order to evaluate side effects of the drugs, a second dose of the aerosols, 8-10 times higher than the first one, was given after 30 min. The effects were measured in terms of VC, FEV1.0, PEF and heart rate. All the substances caused a significant increase in spirometric values within 1.5 min, the results with isoprenaline being slightly better than those with terbutaline. An increased heart rate was observed after the first dose of isoprenaline whereas no further increase was found after the higher dose. Two patients complained of palpitations, one after isoprenaline and one after rimiterol. No other side effects were recorded. It is concluded that there is a small, clinically insignificant, difference in the onset of action of isoprenaline compared with that of the selective beta2-stimulating aerosol, terbutaline.

Topics: Adult; Aged; Asthma; Bronchodilator Agents; Bronchospirometry; Catechols; Clinical Trials as Topic; Drug Evaluation; Female; Heart Rate; Humans; Isoproterenol; Male; Middle Aged; Piperidines; Terbutaline; Time Factors

1 Ten asthmatic children received on two separate occasions rimiterol (500 microgram) and orciprenaline (1.5 mg) as aerosols in a double-blind, crossover design trial. Respiratory parameters (FEV1, FVC and PEFR) and pulse rate were recorded for 60 min after each administration. 2 Rimiterol produced effective bronchodilation in children with negligible cardiac stimulation. It differed from orciprenaline in that the peak bronchodilator effect was not maintained during the 60 min observation period. 3 Rimiterol is a selective, short-acting, sympathomimetic bronchodilator in children.

Topics: Aerosols; Asthma; Catechols; Child; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Metaproterenol; Piperidines; Pulse; Respiratory Function Tests

Topics: Adult; Aerosols; Aged; Airway Obstruction; Albuterol; Bronchodilator Agents; Catechols; Forced Expiratory Volume; Heart Rate; Humans; Middle Aged; Piperidines; Placebos; Receptors, Adrenergic; Receptors, Adrenergic, beta

In a double-blind long-term study, regular inhalations of a short-acting selective beta2-stimulator, rimiterol, was compared with a long-acting one, terbutaline. The trial comprised 60 patients with chronic obstructive lung disease, all patients were on a small dose of an oral beta2-stimulator. Both drugs were regularly given in aerosol form with a minimum dose of three inhalations three times daily. The main purpose was to study subjective and objective side effects. Haematological, hepatic and renal functions were screened for toxicity. Consumption of spray was recorded. No side effects occurred. There was no evidence of development of isoprenaline resistance. The consumption of spray was the same in both groups. In this study, regular inhalation treatment of rimiterol seemed to be as effective as terbutaline in long-term bronchodilator therapy.

Topics: Aerosols; Asthma; Bronchitis; Catechols; Chronic Disease; Drug Evaluation; Female; Humans; Isoproterenol; Lung Diseases, Obstructive; Male; Piperidines; Pulmonary Emphysema; Terbutaline

Topics: Absorption; Administration, Oral; Aerosols; Albuterol; Animals; Asthma; Bronchodilator Agents; Catechols; Clinical Trials as Topic; Half-Life; Hemodynamics; Humans; In Vitro Techniques; Injections, Intravenous; Isoproterenol; Kinetics; Muscle Contraction; Myocardial Contraction; Organ Specificity; Piperidines; Terbutaline; Tremor

1. Using the same technique of administering drugs by intermittent positive-pressure ventilation as used in previous studies a source of contamination of solutions nebulized was discovered. This was rectified by using a new ventilator and completely separate patient circuits for each solution nebulized. 2 Salbutamol 0.5% and 0.25% solutions achieved the same degree of bronchodilatation, but there was a significantly greater increase in heart rate produced by salbutamol 0.5%. 3 Rimiterol 0.5% and salbutamol 0.25% produced similar peak mean improvements in FEV and also induced the same degree of tachycardia, but the duration of these effects were significantly shorter in the case of rimiterol. 4 The sustained degree of bronchodilatation achieved by salbutamol 0.25% could not be mirrored by giving two doses of rimiterol 0.5%, the second dose 2 h after the first. 5 Rimiterol 0.5% induced a degree of tachycardia which was similar in peak effect to that observed after salbutamol 0.25%. However, in the controls the second dose of rimiterol, given 2 h after the first, was responsible for only a small increase in heart rate which was not significantly different than that after saline in the other three treatment groups.

Topics: Adult; Aged; Albuterol; Asthma; Catechols; Female; Forced Expiratory Volume; Heart Rate; Humans; Intermittent Positive-Pressure Breathing; Male; Middle Aged; Piperidines; Positive-Pressure Respiration; Time Factors

Topics: Animals; Asthma; Catechols; Clinical Trials as Topic; Drug Evaluation; Drug Evaluation, Preclinical; Humans; Lung Diseases, Obstructive; Piperidines

1 The bronchodilating efficacy and the degree of beta2-adrenoceptor selectivity of rimiterol, salbutamol and isoprenaline were determined in seven subjects who exhibited histamine-induced bronchoconstriction. 2 Rimiterol, 0.5 (high dose) and 0.05 (low dose) mug kg-1 min-1, salbutamol, 0.3 and 0.03 mug kg-1 min-1, isoprenaline, 0.05 and 0.005 mug kg-1 min-1 and placebo were administered by a single intravenous injection over 6 min, and the protection against histamine-induced bronchoconstriction, changes in heart rate, pulse pressure and skeletal muscle tremor were measured. 3 Rimiterol (98%), salbutamol (96%) and isoprenaline (69%) protected against histamine-induced bronchoconstriction. For these ventilatory responses, there was a heart rate increase of 31.9, 24.7 and 44.3 beats/min for rimiterol, salbutamol and isoprenaline respectively. The three drugs produced similar increases in pulse pressure and tremor. 4 Significant dose-responses were obtained for all the parameters with each drug. 5 Isoprenaline was approximately 7 and 5 times as potent as rimiterol and salbutamol respectively in bronchodilator action when equimolar doses were compared. Similarly, isoprenaline was approximately 14 and 10 times as potent in increasing the heart rate as rimiterol and salbutamol respectively. 6 Rimiterol, a new beta-adrenoceptor stimulating drug, is an effective bronchodilator and has similar beta2-adrenoceptor selectivity to salbutamol when administered intravenously. The relative potencies and degrees of beta2-adrenoceptor selectivity of these drugs depend partly on their route of administration.

Topics: Adult; Albuterol; Catechols; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Isoproterenol; Male; Middle Aged; Piperidines; Receptors, Adrenergic; Receptors, Adrenergic, beta

Topics: Aerosols; Aged; Asthma; Bronchodilator Agents; Catechols; Circadian Rhythm; Clinical Trials as Topic; Female; Heart Rate; Humans; Hydrogen-Ion Concentration; Male; Methanol; Middle Aged; Oxygen; Partial Pressure; Piperidines

The bronchodilating efficacy and the degree of beta2-selectivity of rimiterol, salbutamol and isoprenaline were determined in seven asthmatic patients. Rimiterol, 0.5 (high dose) and 0.05 mug/kg/min (low dose), salbutamol, 0.3 and 0.03 mug/kg/min, isoprenaline, 0.05 and 0.005 mug/kg/min, and placebo were administered by a single intravenous injection over 6 minutes in a double-blind trial. Airway resistance, heart rate, blood pressure and skeletal muscle tremor were measured before and at various times for 2 hours after each injection. The high doses of rimiterol (37%), salbutamol (37%) and isoprenaline (32%) produced immediate and effective bronchodilatation. The duration of action of rimiterol and isoprenaline was similar and shorter than that of salbutamol. For these ventilatory responses there were heart rate increases of 32, 20 and 40 beats/min for rimiterol, salbutamol and isoprenaline, respectively. The three drugs produced similar increases in pulse pressure and tremor. Dose-responses were obtained for each drug with all parameters measured and significant differences at various times found. Isoprenaline was approximately 8 and 5 times as potent as rimiterol and salbutamol, respectively, in bronchodilator action, when equimolar doses were compared. Similarly, isoprenaline was approximately 16 and 12 times as potent in increasing the heart rate as rimiterol and salbutamol, respectively. For an equal bronchodilator action, isoprenaline increased the heart rate 2 and 2.5 times more than rimiterol and salbutamol, respectively. Rimiterol is an effective, short-acting bronchodilator, with similar beta2-selectivity to salbutamol, when administered intravenously to asthmatic patients. The relative potencies and degrees of beta2-selectivity of these drugs depend partly on their route of administration.

Topics: Adrenergic beta-Agonists; Adult; Albuterol; Asthma; Blood Pressure; Bronchi; Bronchodilator Agents; Catechols; Clinical Trials as Topic; Dose-Response Relationship, Drug; Forced Expiratory Volume; Heart Rate; Humans; Isoproterenol; Male; Middle Aged; Piperidines; Placebos; Tremor; Vital Capacity

A comparison between the acute effects of rimiterol (0.5 mg) and salbutamol (0.2 mg.) has been made using metered dose aerosols. In this dosage it was found that the peak effect of the two drugs was the same but that the effect of rimiterol was less prolonged than that of sulbutamol. No increase in blood pressure occurred and heart rate changes were minimal after both drugs. Rimiterol is an acceptable alternative to the short-acting isoprenaline but lacks the cardiovascular effects of isoprenaline and is an alternative to salbutamol where very prolonged action is unnecessary.

Topics: Adult; Aerosols; Airway Obstruction; Albuterol; Asthma; Blood Pressure; Bronchi; Bronchitis; Bronchodilator Agents; Cardiovascular System; Catechols; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Isoproterenol; Male; Methanol; Middle Aged; Piperidines; Respiratory Function Tests; Respiratory Therapy

The bronchodilating efficacies and beta2-adrenoceptor selectivities of rimiterol (0.2, 0.1, and 0.05 mug kg-minus1 min-minus1) and sal-utamol (0.1, 0.5, and 0.025 mug kg-minus1 min-minus1), intravenously infused for one hour, were determined in five patients with chronic asthma. Each drug infusion produced and maintained a dose-related improvement in forced expiratory volune in one second (FEV1). A further increase in FEV1 was produced by inhalation of the same drug by pressurized aerosol at the end of each infusion, which suggested that no resistance had occurred. Similar dose-related increases in heart rate, pulse pressure, and skeletal muscular tremor were produced by each drug. Peak heart rate increases varied greatly between individuals, ranging from 12 to 30 beats/min with the high doses but always less than 10 beats/min with the low doses of each drug. On rimiterol the heart rate reached equilibrium earlier during the infusions and declined more rapidly after they had stopped, thus providing an accurate means for monitoring dosage. Rimeterol with its short half life-a desirable property for an intravenous drug with respect to safety-may prove to be a valuable bronchodilator in severe asthma when intravenous infusions are indicated.

Topics: Albuterol; Asthma; Blood Pressure; Bronchodilator Agents; Catechols; Dose-Response Relationship, Drug; Forced Expiratory Volume; Heart Rate; Humans; Injections, Intravenous; Male; Methanol; Middle Aged; Muscles; Piperidines; Pulse; Respiratory Therapy; Vital Capacity

Topics: Adrenergic beta-Agonists; Adult; Aerosols; Amino Alcohols; Bronchial Spasm; Butylamines; Catechols; Clinical Trials as Topic; Electrocardiography; Female; Heart Rate; Histamine; Humans; Isoproterenol; Male; Methanol; Phenethylamines; Piperidines; Respiration; Skin Temperature; Sympathomimetics; Vasodilator Agents

Topics: Adrenergic beta-Agonists; Adult; Aerosols; Amino Alcohols; Bronchi; Bronchodilator Agents; Catechols; Dose-Response Relationship, Drug; Heart Rate; Humans; In Vitro Techniques; Infant, Newborn; Isoproterenol; Lung Diseases; Methanol; Middle Aged; Muscle Contraction; Muscle, Smooth; Piperidines; Placebos; Respiration; Spirometry; Stimulation, Chemical; Time Factors

We have used a short-acting beta 2-adrenoceptor agonist, rimiterol hydrobromide, to allow a larger dose of allergen to be administered to previous single "early allergen responders" to investigate if an increased dose of allergen could induce a late asthmatic response (LAR) and whether this would influence the subsequent level of allergen-acquired nonspecific bronchial hyperresponsiveness. Pretreatment with inhaled rimiterol hydrobromide 400 microgram enabled an increase in allergen dose inhaled by a geometric mean of 8.9-fold (range, 2 to 29.1) in eight atopic subjects with mild asthma who initially were classified as single early responders with a maximal fall in FEV 3 to 8 h after allergen challenge (Lmax) of less than 15% from baseline value. The magnitude of the early asthmatic response was similar to that obtained on the control day when allergen challenge was performed in the absence of rimiterol hydrobromide. Five subjects were converted to dual allergen responders with Lmax of greater than 15% from premedication baseline value. For the whole group, there was a significant increase in the magnitude of LAR whether calculated as Lmax (p less than 0.05) or as area under the FEV1 time response curve between 3 and 8 h postchallenge (p less than 0.01). The provocation concentrations of methacholine causing a 20% fall in FEV1 (PC20) at 8 h postchallenge were significantly reduced on both days when compared with the corresponding prechallenge values (p less than 0.05 on control day, p less than 0.01 on rimiterol day). However, despite the increase in the magnitude of LAR on the rimiterol day, the reduction in postchallenge PC20 did not differ significantly from that occurring on the control day.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Allergens; Asthma; Bronchi; Bronchial Provocation Tests; Catechols; Female; Forced Expiratory Volume; Humans; Male; Methacholine Chloride; Methacholine Compounds; Middle Aged; Piperidines; Spirometry; Time Factors

Topics: Animals; Catechol O-Methyltransferase; Catechols; Corticosterone; Female; Formaldehyde; Guinea Pigs; In Vitro Techniques; Kinetics; Metanephrine; Muscle, Smooth; Piperidines; Protein Binding; Trachea

Topics: Aerosols; Asthma; Bronchi; Catechols; Forced Expiratory Volume; Humans; Piperidines

Rimiterol hydrobromide (Pulmadil) has been shown to have a dose-related bronchodilator effect; the optimum dose by inhalation appears to lie between 200 and 1,000 microgram. When given to a group of asthmatic patients at 'recommended' and 5--10 times 'recommended' dose by aerosol, cardiovascular effects were minimal and of a magnitude similar to that of salbutamol given in the same dosages to the same patients. The very rapid bronchodilator effect of rimiterol would appear to make the drug particularly suitable for the treatment of patients with intermittent asthmatic attacks, before exercise in patients with exercise-induced asthma and for bronchodilatation before using inhaled sodium cromoglycate or corticosteroid aerosols.

Topics: Aerosols; Albuterol; Asthma; Blood Pressure; Bronchial Spasm; Catechols; Heart Rate; Humans; Peak Expiratory Flow Rate; Piperidines

1. Rimiterol and isoprenaline produced significant dose-related increases in cardiac output. 2. These changes in cardiac output were accompanied by increases in heart rate and myocardial oxygen consumption which were similar for each drug and dose-related. 3. Isoprenaline in contrast with rimiterol produced direct coronary vasodilation, i.e. coronary vasodilation in excess of that required to meet increases in myocardial oxygen demands. 4. It is suggested that the beta-adrenergic receptors in the human coronary vasculature are mainly of the beta1 type. 5. Rimiterol, because it does not produce direct coronary vasodilation may be preferable to isoprenaline in the treatment of low-cardiac output syndrome where there is regional myocardial ischaemia, since it would be less likely to produce a "coronary steal" effect.

Topics: Adult; Catechols; Coronary Circulation; Hemodynamics; Humans; Isoproterenol; Male; Middle Aged; Myocardium; Oxygen Consumption; Piperidines; Regional Blood Flow

Topics: Animals; Catechols; Female; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Muscle Relaxation; Piperidines; Receptors, Adrenergic, beta; Stimulation, Chemical; Trachea

Ten patients undergoing diagnostic bronchoscopy had radioisotopically labelled drugs put directly into their bronchi; two received sodium cromoglycate, two salbutamol, three salmefamol and three rimiterol. All four drugs were rapidly absorbed but higher peak plasma levels per unit dose were seen with sodium cromoglycate and salbutamol than with the other two drugs. It is suggested that the lung metabolizes salmefamol and rimiterol but does not metabolize salbutamol or sodium cromoglycate.

Topics: Absorption; Adult; Aged; Albuterol; Catechols; Cromolyn Sodium; Ethanolamines; Humans; Lung; Middle Aged; Piperidines

Topics: Administration, Oral; Adrenergic beta-Agonists; Aerosols; Asthma; Bronchodilator Agents; Bronchoscopy; Catechols; Humans; Methanol; Piperidines

1. The actions of rimiterol [erythro(3,4-dihydroxyphenyl, 2-piperidyl methanol hydrobromide)], a new sympathomimetic bronchodilator, have been compared with those of salbutamol and laevoisoprenaline on the heart and lungs, and on contractions of the soleus muscle of cats under chloralose anaesthesia.2. Rimiterol and salbutamol injected intravenously were about equipotent in all tests, and were about 8 times less potent than laevoisoprenaline both in opposing the bronchoconstrictor action of 5-hydroxytryptamine, and in decreasing the tension and degree of fusion of incomplete tetanic contractions of the cat soleus muscle. They were about 19 times less potent than laevoisoprenaline in increasing heart rate.3. The effect on the soleus muscle is considered to be analogous to the muscle tremor that often occurs in man, and the results therefore suggest that systemic administration of bronchodilator doses of rimiterol, like salbutamol, may produce muscle tremor as an unwanted side-effect.4. When equipotent doses to oppose 5-hydroxytryptamine-induced bronchospasm were compared, rimiterol and salbutamol produced less tachycardia than did laevoisoprenaline. In order to match the tachycardia produced by laevoisoprenaline, the doses of rimiterol or salbutamol had to be increased about two and a half times. This safety margin for salbutamol in the cat is considerably less than that reported by others for different species, which suggests that beta(1)- and beta(2)-adrenoceptors may be less clearly differentiated in the cat than they are in other laboratory animals.

Topics: Amino Alcohols; Animals; Blood Pressure; Bronchodilator Agents; Catechols; Cats; Female; Heart; Heart Rate; Injections, Intravenous; Isoproterenol; Lung; Male; Methanol; Muscle Contraction; Muscles; Piperidines; Serotonin Antagonists; Stimulation, Chemical