Treatment of apneustic respiratory disturbance with a serotonin-receptor agonist

Apneusis is a disturbance of respiratory rhythm characterized by severely prolonged inspiratory effort. It may occur after damage to the respiratory network within the lower brain stem and pons from an overdose of central nervous system depressants, blockade of glutamate receptors, asphyxia, hypoxia, or ischemia. Experimental studies conducted on laboratory mammals, such as anesthetized cats and rats, suggest that apneusis results mostly from depression of glutamatergic synaptic processes that are necessary for activation of inhibitory mechanisms that terminate inspiration. The impairment of synaptic transmission leads to prolonged inspiratory efforts and apneustic discharges of brainstem respiratory neurons. Apneustic patterns can be consistently converted to normal by administration of serotonin type 1A (5-HT1A) receptor agonists. This observation encouraged a treatment of severe apneusis with buspirone, an agonist for 5-HT1A receptors, in a child after neurosurgery for an astrocytoma in the pons and medulla oblongata. Oral administration of buspirone produced a prompt and highly effective remission of apneusis without side effects. Treatment with 5-HT1A agonists, therefore, might offer a novel and effective pharmacotherapy against apneustic disturbances of breathing.