![]() ![]() ![]() The authors fully expect that hypnotic agents will continue to utilize the properties of GABA A receptor agonism, melatonin receptor agonism, or histamine receptor antagonism well into the future. Similarly, if ramelteon is taken, melatonin receptors are also directly stimulated and the switch is moved as if endogenous melatonin is present. Melatonin is released as the SCN signals darkness is present and then the simple switch is pushed towards promoting sleepiness. The suprachiasmatic nucleus (SCN) is similar to a master switch which helps to control and guide the simple ‘sleep–wake switch’. This drug agonizes the melatonin type 1 (MT1) and melatonin type 2 (MT2) receptors and this activity is thought to dampen reticular activating system monoamines (norepinephrine, serotonin, and dopamine) from arousing the cortex and to correct circadian rhythm activity respectively. The final existing prescription hypnotic agent, ramelteon utilizes a unique mechanism and facilitates the melatonin system’s activity. Recently, the aged tricyclic antidepressant doxepin has been approved as the first antihistamine prescription sleeping agent, being used at low doses to induce sleep. Psychopharmacologists often use off-label, sedating antidepressants such as trazodone, mirtazapine, or amitriptyline to induce sleep as they typically utilize H1 receptor antagonism as well. Diphenhydramine, chlorpheniramine, and doxylamine have all been approved for over-the-counter hypnotic use and are often incorporated into pain, cold, and influenza remedies. Blocking histamine-1 (H1) receptors successfully dampens cortical arousal, and fatigue and sleepiness result. Agents that are largely used ‘over-the-counter’, or prescribed as off-label treatments, utilize the antagonism of the histamine system. These GABA A receptor-enhancing drugs effectively turn on sleep promoting areas of the brain and inhibit arousal centers. Approved hypnotic agents have relied heavily on manipulating the GABA A receptor and its neurocircuitry. When one side of the switch is active patients are awake and alert when the other side is active patients go to sleep. One prototypical circuit is the ‘sleep–wake switch’. Neurotransmitter systems (histamine, acetylcholine, norepinephrine, serotonin, orexin, and dopamine) may promote alertness, wakefulness, and vigilance when activated and contrarily could become hypnotic and sleep inducing if they were antagonized, thus removing arousal in the CNS. The need for treating insomnia as a primary entity or as a secondary symptom of mental or medical disorder continues, as does the need to find agents that are more specific for sleep–wake neurocircuitry with less risky adverse effects. GABA A receptors are ubiquitous and facilitating them is akin to a blanketing effect where neuronal dampening occurs across the CNS, not necessarily localized to sleep–wake centers. The development of tolerance and the need for progressively higher doses, physiological and psychological dependence on medications, and potential withdrawal from medications can cause significant difficulties for patients. The use of GABA A-modulating agents has been effective for treating insomnia, but at a cost of an adverse effect profile consisting of addiction, over-sedation, psychomotor impairment, respiratory suppression, and somnambulism. The classic benzodiazepine hypnotic agents work through both of these mechanisms, as do the barbiturates and ethanol, and will be further discussed later in this article. Alternatively, if GABA A receptor activity increases in sleep-promoting centers, then sleep prevails more directly. ![]() Classically, if GABA A receptor PAM occurs in wakefulness brain centers, alertness falters and sleep prevails. Here, gamma-amino butyric acid (GABA) neuronal activity is enhanced by positive allosteric modulation (PAM). The most widely used prescription hypnotic agents since the 1960s have utilized the same mechanism of action to induce sleep. This offers an opportunity for clinicians to engage in rational polypharmacy in order to treat insomnia alone or when part of a comorbid condition. There are clearly indicated hypnotic agents and many off-label medications that may be used to improve sleep duration or quality. It continues to be a clinical target symptom of interest for clinicians who treat psychiatric conditions, medical conditions, pain conditions, or associated sleep disorders. Insomnia can be an acute predictor of who will ultimately attempt suicide. Insomnia is a commonly induced side-effect as well. Insomnia is a common disorder and, in the realm of psychiatric care, one of the most common residual symptoms in major depression after antidepressant treatment is offered.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |