Muscarinic Antagonist - Effects

Effects

Scopolamine and atropine have similar effects on the peripheral nervous system, however, scopolamine has greater effects on the Central Nervous System (CNS) than atropine due to its ability to cross the blood–brain barrier. At higher than therapeutic doses, atropine and scopolamine cause CNS depression characterized by amnesia, fatigue and reduction in rapid eye movement sleep. Hyoscine has anti-emetic activity and is therefore used to treat motion sickness.

Antimuscarinics are also used as anti-parkinsonian drugs. In Parkinsonism, there is imbalance between levels of acetylcholine and dopamine in the brain, involving both increased levels of acetylcholine and degeneration of dopaminergic pathways (nigrostriatal pathway). Thus, in Parkinsonism there is decreased level of dopaminergic activity. One method of balancing the neurotransmitters is through blocking central cholinergic activity using muscarinic receptor antagonists. In addition to increased activity to dopaminergic neurons from anticholinergics, antagonists of the muscarinic-acetylcholine receptors produce a sense of happiness and euphoria. This led to the discovery of various tricyclic antidepressants

Atropine acts on the M2 receptors of the heart and antagonizes the activity of acetylcholine. It causes tachycardia by blocking vagal effects on the sinoatrial node. Acetylcholine hyperpolarizes the sinoatrial node which is overcome by MRA and thus increases the heart rate. If atropine is given by intramuscular or subcutaneous injection it causes initial bradycardia. This is because by i.m/s.c it acts on presynaptic M1 receptors (autoreceptors). Intake of acetylcholine in axoplasm is prevented and the presynaptic nerve releases more acetylcholine into the synapse which initially causes bradycardia.

In the atrioventricular node, the resting potential is abbreviated which facilitates conduction. This is seen as a shortened PR-interval on an electrocardiogram.

It has an opposite effect on blood pressure. Tachycardia and stimulation of the vasomotor center causes an increase in blood pressure. But due to feed back regulation of the vasomotor center, there is fall in blood pressure due to vasodilation.

Important muscarinic antagonists include atropine, hyoscine, ipratropium, tropicamide, cyclopentolate and pirenzepine.

Muscarinic antagonists such as ipratropium bromide can also be effective in treating asthma since acetylcholine is known to cause smooth muscle contraction; especially in the bronchi.