Neurophysiology of Basic Molecules Affecting Sleep and Wakefulness Mechanisms, Fundamentals of Sleep Pharmacology

Abstract

As part of the biological rhythm, the human brain has a healthy functioning with the ability to differentiate between day and night hours in any given day (sleep rhythm, life rhythm). From the control of hormone levels to muscle tonus, from the regulation of respiratory rate to the content of our thoughts, sleep has an impact on all bodily and cognitive functions. It is not surprising to see such effects of sleep on the body as it leads to significant changes in the electrical activity of the brain in general. Electrical signal changes in the brain (sleep-wakefulness rhythm) are regulated by neurohormonal molecules and their receptors in the body. Neurotransmitters that control sleep and wakefulness can be listed as “Glutamate, Acetylcholine, Histamine, Norepinephrine and GABA”. Main hormones are: Melatonin, Corticotropin Releasing Hormone (CRH), cortisol, prolactin, Growth Hormone (GH), Insulin like Growth Factor (IGF-1, Somatomedin-C), Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), progesterone, estrogen, testosterone, catecholamines, leptin and neuropeptide Y″. The effects of pharmacological agents on sleep and wakefulness cycles are materialized through the following molecules and their receptors: Hypnotics (GABA A agonists, benzodiazepines, gabapentin, tiagabine), sedative antidepressants (tricyclic antidepressants, trazadone, mitrazapine), antihistamines, medications used for the treatment of sleeplessness (melatonin and melatonin analogues), amphetamine (most commonly used stimulant), secretion of monoamines (dopamine), non-amphetamine stimulants used in the treatment of hypersomnia and narcolepsy (modafinil, bupropion, selegiline, caffeine) and other substances (alcohol, nicotine, anesthetics). To the extent we can conceptualize the physiological mechanisms of these basic molecules listed above and the regions they affect, we can appreciate the effects of these substances on sleep physiology and sleep disorders.