[Piperidine in the brain: its neurobiological significance]

Piperidine (Pip) is a normal constituent in mammalian brain, affects synaptic mechanism in the CNS, and influences neural mechanisms governing regulation of emotional behavior and extrapyramidal function. In addition, there are enzyme systems within the brain that synthesize and metabolize Pip, and uptake and storage mechanisms for Pip are found in the nerve endings. Pip is highly concentrated in the pituitary and pineal glands, hippocampus and caudate nucleus among the regions of the brain. Levels of Pip in the brain show physiological variations associated with environmental changes. The levels increase significantly under deep anesthesia. The study on the time relations of the change in brain levels of Pip and the anesthetic activity demonstrates that the level increases prior to the loss of the righting reflex and that the elevated level declines prior to the reappearance of the reflex. Furthermore, Pip levels in the lower brainstem reticular formation show sleep-related changes during REM sleep deprivation and REM sleep rebound that followed. Direct administration of Pip into the hippocampus and amygdala of cats with chronically implanted electrodes and a cannula caused resting and calmness in small doses, and seizure discharge accompanied by hyperemotionality in large doses. Administration into the pontine reticular formation induced REM and NREM sleep. Iontophoretic application produced the excitation and inhibition of single neuron activities in the cerebral cortex, hippocampus, caudate nucleus, cerebellum, and pituitary in anesthetized rats. With no anesthesia, Pip caused the inhibitory action in a higher percentage of the neurons studied, compared with the result obtained under anesthesia. Pip-induced excitation and inhibiton were blocked by tetramethylammonium but little affected by scopolamine. The kinetic study of Pip-induced Cl- current in internally perfused neurons of Aplysia, by using the 'concentration camp' and voltage clamp techniques, revealed that Pip acted on at least two components of nicotinic receptor-Cl- channel complex, and further that Pip could discriminate between the transient and the persistent components of ACh-induced Cl- current. These findings suggest that Pip may have close connections with neuroendocrine as well as neuronal functions, and further, with the mechanisms underlying sleep-consciousness and emotional function. Because of piperidine's multiplex pharmacological activities, the study of piperidine may provide a clue to the discovery of new active drugs and to the elucidation of causes of pathological states relating to the brain function.