4- , bronchodilatory

The alkaloid vasicine was first isolated from Adhatoda vasica in 1925 but the structure (996) was elucidated only after a great amount of work, culminating in two independent syntheses in 1935 (B-53MI21301). It was made subsequently by a simple route from 2-aminobenzaldehyde and 4-amino-2-hydroxybutyraldehyde (994) followed by dehydration of the tricyclic intermediate (995) (60TL(25)44>. Vasicine has bronchodilatory activity of a low order. Two related unnamed alkaloids (997) and (998) were obtained in 1965 from members of the Araliaceae family, viz. Mackinlaya subulata and M. macrosciadia both had been synthesized earlier (66AJC151). 

In the aitways, inhibition of PDE4 is much more antiinflammatory than bronchodilatory. Although effective in animal experiments, the neuronal and gastric side effects of PDE4-inhibitors have so far impeded their use in humans. Two new orally active PDE4-inhibitors (roflumilast, cilomilast) have shown some effectiveness in advanced clinical trials, but have not yet been approved. 

Histamine stimulates bronchiolar smooth muscle contraction through activation of Hj-receptors. A much smaller bronchodilatory response is evoked by stimulation of Hz-receptors. Asthmatics are generally more sensitive to the bronchoconstrictor actions of histamine than are nonasthmatics. 

A pharmacological effect may be observed only when food contains elevated concentrations of potent therapeutics, as in the case of the -blocker carazo-lol whose residues in tissues caused sedation residues of the -agonist clenbuterol that produced bronchodilatory action and residues of the anthelminthic ivermectin that produced antiparasitic activity (51). 

Labdane type diterpenes obviously exhibit a wide spectrum of actions. Primarily forskolin exhibits (a) antihypertensive properties, lowering blood pressure in different animal species through a vasodilatory effect (b) positive inotropic effects in cardiac muscle and (c) bronchodilatory effects [155] and (d) pressure-lowering properties [244]. 

Methylpiperbetol Piper betle (Piperaceae) bitter, bronchodilatory] PAF-R antagonist (5) [PAI -... 

AChE [abortefacient, anthelmintic, bronchodilatory, cholinergic, hypotensive, respiratory stimulant, uterotonic]... 

The 5-isomer of albuterol has been shown to oppose the bronchodilatory effects of the eutomer, /J-albuterol and may therefore contribute to paradoxic bronchospasm and the occurrence of severe reagenic-like reactions seen with racemic albuterol. 

Verheijen-Breemhaar L, Bogaard JM, Hilvermg C. Comparison of the bronchodilatory action and side-effects of ipratropium bromide and thiazinamium methyl sulphate a long-term, double-bhnd, crossover trial in patients with chronic bronchitis. Pharmatherapeutica 1982 3(3) 180-7. 

The hexahydroazepino[2,l-6]quinazolinone 306 showed the maximum bronchodilatory activity from among the homologous tricyclic derivatives 99 ( = 0-2). ... 

Clenbuterol, a P2 adrenoceptor agonist, is sometimes used in pregnant mares with lower airway disease for its bronchodilatory effects. This drug has been found to have minimal effects on fetal heart rate when administered i.v. to mares in the last trimester of pregnancy. The effects on fetal health have not been established. 

Ketamine is not a significant respiratory depressant and the ventilatory response to hypoxia is maintained. Ketamine has a bronchodilatory effect subsequent to sympathetic stimulation. Airway reflexes are well maintained after ketamine administration. However, since ketamine is not used as... 

Most albuterol sulfate preparations contain an equimolar, racemic mixture of the (R)- and (S)-stereoisomers (Page Morley 1999). (R)-albuterol has bronchodilator and bronchoprotec-tive activity. (S)-Albuterol does not activate P2 adrenoceptors and does not modify the activation of these receptors by (R)-albuterol. (S)-Albuterol is metabolized more slowly than (R)-albuterol and is retained preferentially in the airways. Until recently, (S)-albuterol was considered biologically inert however, it has been shown to intensify allergic bronchospasm and eosinophilic activation in laboratory animals and appears to have the potential to induce paradoxical reactions in some asthmatic patients. In horses, (S)-albuterol does not have bronchodilatory activity and stimulates acetylcholine release via prejunctional 2 adrenoceptor stimulation (Zhang et al 1998). Levalbuterol (homochiral (R)-albuterol) has been marketed recently and reportedly dramatically reduces the incidence of the side-effects associated with racemic albuterol in some patients. 

Chiarino et al. [43] described some potent and remarkably selective (3o-adrenoceptor agonists in a series of l-(3-substituted-5-isoxazolyi)-2-alkyl-aminoethanol derivatives in which the isoxazole ring replaces the catechol moiety in the (3-adrenergic compounds. From this series, the compound broxaterol (1) displayed a marked selectivity toward (32-receptors of the trachea and was selected for further development as a potential bronchodilatory agent. 

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