Bronchodilator activity

Cromakalim. Cromakalim has along half-life (254). Cromakalim at an oral dose of 1.5 mg ia humans significantly lowers blood pressure 19/12 mm Hg (systohc/diastoHc pressure). It iacreases reaal blood flow, PRA, and heart rate. Cromakalim has bronchodilating activity that is beneficial for hypertensive asthmatic patients. Because of some undesirable effects seen ia cardiac papillary muscles of animals oa long-term treatmeat, future clinical trials are to be carried out usiag the active enantiomer, lemakalim (BRL 38227). 

A derivative of an isomeric azapurine ring system interestingly exhibits bronchodilator activity, possibly indicating interaction with a target for theophylline. The starting pyridazine 97 is available from dichloro compound 96 by sequential replacement of the halogens. Treatment of 97 with formic acid supplies the missing carbon and cyclizes the intermediate formamide with consequent formation of zindotrine (98) [16]. 

The xanthine derivatives, although a different class of drag, also have bronchodilating activity by means of their direct relaxation of tlie smooth muscles of the bronchi. 

FIGURE 11 Duration of bronchodilator activity in an animal model Anesthesized guinea pigs received 1 ymol/kg of terbutaline, free or in liposomes, via intracheal instillation at time zei o. Bronchodilator activity was measured as the reduction in histamine-induced airway resistance. Histamine (10 yg/kg) was administered i.v. prior to each resistance measurement, o saline (n = 3) free drug (n = 3) a liposomal drug (n = 4). (Courtesy of Liposome Technology, Inc., Menlo Park, California.)... 

A report dealing with the bronchodilator activity and transamination reactions of 4-aminopyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides has been published . 

Bronchodilator activity, antihistaminic, and analgesic effects have been confirmed. Hydroxyzine has antispasmodic properties, and an antiemetic effect has been demonstrated. 

Twenty years ago theophylline (Theo-Dur, Slo-bid, Uniphyl, Theo-24) and its more soluble ethylenedi-amine salt, aminophylline, were the bronchodilators of choice in the United States. Although the p2-adreno-ceptor agonists now fill this primary role, theophylline continues to have an important place in the therapy of asthma because it appears to have antiinflammatory as well as bronchodilator activity. 

Although atropine and related compounds possess bronchodilator activity, their use is associated with the typical spectrum of anticholinergic side effects (see Chapter 13), and they are no longer used in the treatment of asthma. To improve the clinical utility of anticholinergics, quaternary amine derivatives of atropine were developed. By virtue of their positive charge, these drugs are absorbed poorly across mucosal surfaces and thus produce fewer side effects than atropine, especially when given by inhalation. 

Bronchodilator activity. Petroleum ether extract of the aerial parts, administered orally to adults of both sexes, was inac-... 

Though better tolerated, significantly less bronchodilating activity vs theophylline. Serious dosing errors possible if dyphylline monitored with theophylline serum assays... 

Incorporation of a piperazine function on the heterocyclic ring leads to a compound in which bronchodilator activity predominates. Treatment of the amino-amide (73-1) with trimethyl orthoformate provides the additional carbon atom for the formation of the quinazolone ring in (73-2). Reaction with phosphoms oxychloride in effect converts the ring to its aromatic form (73-3) by locking in the former amide as an enol chloride. Displacement of the halogen with the isobutyryl urethane (73-4) from piperazine affords piquizil (73-5) [82]. 

Q7 Three classes of drug have acute bronchodilator activity ... 

Vasicinone (185) exhibited bronchodilator, - - - weak cardiac stimulant," and potent antianaphylactic activities, whereas vasicine (184) displayed bronchoconstrictor > and cardiac depressant activities. The structure-bronchodilator activity relationship was discussed. Vasicine (184) also had marked respiratory and uterine stimulant activities and a moderate hypotensive activity.Vasicinone (185) was devoid of these activities. ... 

Derksen F, Robinson N, Berney C 1992 Aerosol pirbuterol bronchodilator activity and side-effects in ponies with recurrent ain/vay obstruction (heaves). Equine Veterinary Journal 24 107-112... 

Anticholinergics — Although the precise role of anticholinergics in the treatment of asthma is not yet known, they have been advocated as an alternative to -agonist therapy in patients with cardiac arrhythmias or angina. Ipratropium bromide (14) (Sch. 1000, Atrovent ) by inhalation showed bronchodilator activity comparable with isoproterenol, but had a longer duration of action (4 hr.) with no significant side effects. ... 

Although cannabis was used as a bronchodilator in the nineteenth century, modern human research seems to have been limited to a brief period in the 1970s. Small controlled studies in asthmatic volunteers (Tashkin et al. 1974 Williams et al. 1976 Tashkin et al. 1977) showed that oral, smoked and aerosolised THC had significant bronchodilator activity comparable to that of salbutamol, though slower in onset. Dose-related tachycardia and intoxication occurred at higher doses. An inhaled aerosol avoided systemic absorption of THC but induced cough and chest discomfort, which limited its usefulness. 

Bowden, K. and Wooldridge, K.R.H. (1973) Structure-activity relations. 3. Bronchodilator activity of substituted 6-thioxanthines. Biochem. Pharmacol, 22, 1015-1021. 

The respiratory effects of ketamine are perhaps the best indication for its use. Induction doses of ketamine produce small and transient decreases in minute ventilation, but respiratory depression is less severe than with other general anesthetics. Ketamine is a potent bronchodilator due to its indirect sympathomimetic activity and perhaps some direct bronchodilating activity. Thus, ketamine is particularly well suited for anesthetizing patients at high risk for bronchospasm. 

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