Methacholine

Acetyl-P-methylcholine chloride [62-51-1/, commonly called methacholine chloride, is a parasympathornimetic bronchoconstrictor with clinical efficacy in bronchial asthma (45,46). 

O-Acetyl-p-methylcholine chloride [Methacholine chloride, Amechol, Provocholine, 2-acetoxypropyl-ammonium chloride] [62-51-1] M 195.7, m 170-173", 172-173". It forms white hygroscopic needles from Et20 and is soluble in H2O, EtOH and CHCI3. It decomposes readily in alkaline solns and slowly in H2O. It should be handled and stored in a dry atmosphere. The bromide is less... 

Airway hyperresponsiveness is an exaggerated airway narrowing in response to a variety of unspecific stimuli. It can be measured by bronchial provocation with histamine, methacholine or adenosine. The reason for hyperresponsiveness may be stimulation of sensory nerves that are located within the epithelium. They become easily accessible after denudation of the... 

Some agonists, such as methacholine, carbachol and bethanecol are structurally very similar to ACh (Fig. 6.6). They are all more resistant to attack by cholinesterase than ACh and so longer acting, especially the non-acetylated carbamyl derivatives carbachol and bethanecol. Carbachol retains both nicotinic and muscarinic effects but the presence of a methyl (CH3) group on the p carbon of choline, as in methacholine and bethanecol, restricts activity to muscarinic receptors. Being charged lipophobic compounds they do not enter the CNS but produce powerful peripheral parasympathetic effects which are occasionally used clinically, i.e. to stimulate the gut or bladder. 

H. A. (1986). Ozone-induced change in bronchial reactivity to methacholine and airway inflammation in humans. J. Appl. Physiol. 60, 1321-1325. 

Airway hyperresponsiveness is defined as the exaggerated ability of the airways to narrow in response to a variety of stimuli. Although AHR exists in patients without asthma, it is a characteristic feature of asthma and appears to be directly related to airway inflammation and the severity of asthma.1,3 Treatment of airway inflammation with inhaled corticosteroids attenuates AHR in asthma but does not eliminate it.1 Clinically, AHR manifests as increased variability of airway function. Although not commonly used to diagnose asthma, AHR can be evaluated clinically using a methacholine or histamine bronchoprovocation test. 

Assessment of diurnal variation of PEF may be useful in patients who have asthma symptoms and normal spirometry. When spirometry is equivocal, a 20% or greater decrease in FEV after the administration of methacholine is diagnostic for asthma. A negative bronchoprovocation test with methacholine may help rule out asthma. 

The answer is d. (Hardman, pp 212—213.) Only isoproterenol will lower mean blood pressure, decrease peripheral vascular resistance, and increase heart rate. Methacholine decreases heart rate as does propranolol. Atropine has no action on peripheral resistance. Norepinephrine causes intense vasoconstriction and raises the mean blood pressure. 

Metanilic acid, all6 Methacholine chloride, a49 Methacrolein, m27 Methacrolein diacetate, m32 Methallyl alcohol, m400 Methallyl chloride, cl82... 

Spirometry demonstrates obstruction (forced expiratory volume in 1 second [FEVJ/forced vital capacity less than 80%) with reversibility after inhaled P2-agonist administration (at least a 12% improvement in FEVj). Failure of pulmonary function to improve acutely does not necessarily rule out asthma. If baseline spirometry is normal, challenge testing with exercise, histamine, or methacholine can be used to elicit BHR. 

In sensitized asthmatic individuals, antigen challenge generally causes a Type I (IgE-mediated) immediate hypersensitivity response by release of preformed mediators, including histamine, and prostaglandins, which are responsible for bronchoconstric-tion and increased vascular permeability. Between 2 and 8 hours after the immediate response, asthmatics experience a more severe and prolonged (late phase) reaction that is characterized by mucus hyper-secretion, bronchoconstriction, airway hyperresponsiveness to a variety of nonspecific stimuli (e.g., histamine, methacholine), and airway inflammation characterized by eosinophils. This later response is driven by leukotrienes, chemokines and cytokines synthesized by activated mast cells and Th2 cells. Both proteins and haptens have been associated with these types of reactions. 

Smith, D.L., S.L.Aikman, L.J.Coulby, J.Sutcliffe, and BJ.O Conner. 1994. The attenuation of methacholine-induced bronchoconstriction by salmeterol comparison between an alternative metered dose inhaler propellant GR106642X and chlorofluorocarbons 11 and 12. Eur. Resp. J. 7 (Suppl. 18) 318s. 

Webber, S.E. and Widdicombe, J.G. (1987). The actions of methacholine, phenylephrine, salbutamol and histamine on mucus secretion from the ferret in vitro trachea. Agents and Actions 22 82-85. 

The rate of absorption from an SC injection site may be retarded by immobilization of the limb, local cooling to cause vasoconstriction, or application of a tourniquet proximal to the injection site to block the superficial venous drainage and lymphatic flow. In small amounts, adrenergic stimulants, such as epinephrine, will constrict the local blood vessels and, therefore, slow systemic absorption. Conversely, cholinergic stimulants (such as methacholine) will induce very rapid systemic absorption subcutaneously. Other agents may also alter their own rate of absorption by affecting local blood supply or capillary permeability. 

Guinea pig vas deferens Muscarinic nicotinic or Muscarinic Methacholine/atropine Methacholine/hexamethonium Leach, 1956... 

Rat serosal strip Nicotinic Methacholine/hexamethonium Khayyal, et. al., 1974... 

Materials Required Methacholine chloride 0.4 g glacial acetic acid 50 ml mercuric acetate solution 10 ml 0.1 N perchloric acid and crystal violet solution. 

Calculations The percentage of methacholine chloride in the sample may be calculated by the following expression ... 

In the methacholine challenge test, subjects inhale a drug that can cause the muscles in the small airways to contract. People with asthma will have a reduction in their FEVi after inhaling a low dose of this drug, reflecting increased "irritability" or bronchial h)q5erreactivity. 

Methacholine challenge Increased May show increased reactivity Normal Normal... 

Bronchoconstrictor challenge tests are used to confirm the diagnosis of asthma. AHR to histamine or methacholine (the most commonly used stimuli) is identifiable in virtually all currently symptomatic... 

Town GI, Holgate ST Comparison of the effect of loratadine on the airway and skin responses to histamine, methacholine, and allergen in subjects with asthma. J Allergy Chn Immunol 1990 86 886-893. 

An additional consideration is the safety assessment of agents that will be used for challenge stimuli in the evaluation of pharmacodynamics. In some cases, there is a long history of uneventful clinical use of tests, for example, bronchial challenge with histamine and methacholine. If used in a similar manner, there may be no need to consider performing safety studies in... 

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