Autonomic inhibitor drugs

Spasmolytics. These include atropine (III), which as already explained dilates the pupil of the eye and finds use as a mydriatic in ophthalmology and for the relief of visceral spasm (see also p. 36 and fig. 7). In addition, it has a direct action on the blood vessels causing vasodilatation. It reduces secretions of the salivary, bronchial and sweat glands. Atropine has a peculiar action on the lower motor centres and diminishes the tremor and muscular rigidity of the disease known as Parkinsonism. 

Early synthetic spasmolytics resembled atropine closely, e.g. homatropine (the ester of mandelic acid and tropine (IV)). It may be noted that acetylcholine itself is an ester of a quaternary aminoalcohol and a short-chain organic acid. If the length of the chain is increased, acetylcholine activity decreases and crnn- 

Artane (VII) is a spasmolytic of a rather different type of stractuie  

Sympatholytics. Sympatholytic activity was first detected in the ergot alkaloids. Synthetic substitutes of various kinds have been made with a view to alleviating conditions dependent upon hypertension. 

Tests are made by examining the inhibition caused by the lubstance on the sympathomimetic effects of injected adrenaline and of sympathetic nerve stimulation. Among the recently re-commended anti-adrenaline drugs are iminazole derivatives (e.g. piisool (VIII)) and yff-haloalkylamines (e.g. dibenamine (IX)). The action of dibenamine is almost certainly that of destroying the receptor patches in the effector organ (p. 37). 

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Imipramine Mixed and variable blockade of NET and SERT Like SNRIs plus significant blockade of autonomic nervous system and histamine receptors Major depression not responsive to other drugs chronic pain disorders incontinence obsessive-compulsive disorder (clomipramine) Long half-lives CYP substrates active metabolites Toxicity Anticholinergic, G.-blocking effects, sedation, weight gain, arrhythmias, and seizures in overdose Interactions CYP inducers and inhibitors... 

Amine uptake blockade The drugs that block norepinephrine transporters in the CNS (eg, tricyclics) also inhibit the reuptake of norepinephrine at nerve endings in the autonomic nervous system. Likewise, MAO inhibitors increase NE in sympathetic nerve terminals. In both cases, this can lead to peripheral autonomic sympathomimetic effects. However, longterm use of MAOIs can decrease blood pressure. 

Amrinone is neither a P-adrenergic agonist as dobutamine, and nor an inhibitor of Na — iC-ATPase as digitalis. In the same vein there is no observed a-adrenoreceptor or cholinoreceptor stimulation. Besides, there are no apparent elfects on autonomic ganglia. Evidently, the drug gives rise to enhanced cAMP levels as being responsible for both observed vasodilation and direct positive inotropy. 

Serotonin syndrome occurs primarily in patients taking monoamine oxidase (MAO) inhibitors (see p 269) who also take serotonin-enhancing drugs, such as meperidine (Demerol ), fluoxetine (Prozac ), or other serotonin reuptake inhibitors (SSRIs see Antidepressants, p 88), and is characterized by irritability, rigidity, myoclonus, diaphoresis, autonomic instability, and hyperthermia. It may also occur in people taking an overdose of or combinations of SSRIs even without concurrent use of MAO inhibitors. 

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