Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Sheryl S. Smith in Neurosteroid Effects in the Central Nervous System, 2003
Ethanol-induced LORR in rodents is modified by a large number of neurotransmitters and neuromodulators, including GABA, glutamate, and adenosine. Sedativehypnotic effects produced by high doses of ethanol are potentially mediated by GABAA receptors by either direct or indirect actions. These effects can be enhanced by GABA agonists and blocked by GABA receptor antagonists.68 Several studies show that administration of high doses of 3a,5α-THβ or its precursors to rodents induces a LORR and anesthesia.69,70 Interestingly, VanDoren et al.61 showed that waking cerebral cortical levels of 3a,5α-THβ correlate with duration of ethanolinduced LORR.61 This study suggested a role of neuroactive steroids, including 3a,5α-THP, in the sedative-hypnotic actions of ethanol.
Treatment of Chronic Fatigue Syndrome
Jay A. Goldstein in Chronic Fatigue Syndromes, 2020
The role of the ANS in human pathophysiology is expanding. I have alluded to cortical control of cardiovascular responsiveness, but there is a cerebellar component as well. State changes, such as sleep and wakefulness, modulate baroreceptor tone, probably by serotoninergic mechanisms. The raphe nuclei are involved in migraine headache patients, in whom there is an impairment of sympathetic outflow to the pupil on the affected side.57 Migraines are probably more common in CFS. Thermoreceptive neurons in the preoptic area have been shown to be sensitive to behavioral changes or baroreceptor mechanisms. In multiple system atrophy (MSA), glutamic acid decarboxylase (GAD), a marker for GABA, is decreased, especially in the dentate nucleus. GABA agonists, available in other countries, may therefore be useful.58 A new drug, DL-dops, may increase plasma norepinephrine levels, and somatostatin, which has been occasionally helpful in CFS treatment, ameliorates post-prandial hypotension. These may be employed in MSA. There are infectious causes of autonomic nerve damage, best known in Chagas’ disease, but increasingly recognized in AIDS, in which a significant decline in autonomic function is found. Patients with IBS have been noted to have generalized or patchy anhidrosis, evidence of sympathetic denervation. This finding accords well with the work of Mathias, who has found GnRH receptors in sympathetic ganglia which may be one site of action for Lupron in IBS.59 We have previously discussed the function of the ANS in immunomodulation.
Medication effects on sleep
S.R. Pandi-Perumal, Meera Narasimhan, Milton Kramer in Sleep and Psychosomatic Medicine, 2017
In the 1970s, benzodiazepines became available for the treatment of insomnia. These drugs are nonspecific GABA agonists and have far less overdose danger and abuse potential than barbiturate-like medications. The many drugs in this class are best viewed therapeutically based on their pharmacodynamics (Table 18.2).11 Rapid onset of action is characteristic of flurazepam (Dalmane) and triazolam (Halcion), indicating that both of these agents have excellent sleep-inducing effects. Flurazepam, like diazepam (Valium) and clorazepate (Tranzene), has the characteristic of having active breakdown products. This results in an extraordinarily long active half-life, which can approach 11 days. This prolonged effect in the elderly has been associated with increased automobile accidents and falls with hip fractures.12,13 Withdrawal from long-acting agents can be difficult, with an initial syndrome of insomnia followed by persistent anxiety that may extend beyond the half-life of the agent.
An analysis of the effects of using Zolpidem and an innovative multimodal interdisciplinary team approach in prolonged disorders of consciousness (PDOC)
Published in Brain Injury, 2019
Mark Delargy, Rebecca O’Connor, Alison McCann, Irene Galligan, Heather Cronin, Dee Gray, Caoimhe O’Toole
Zolpidem is a widely prescribed sedative, belonging to the group of drugs known as imidazopiridines. It is a highly selective non-benzodiazepine gamma-aminobutyric acid (GABA) agonist acting on the omega-1 site of the GABA-A receptor, and has a short half-life of 3 hours(13). Singh, McDonald, Dawson, Lewis, Pringle, Smith, Pentland (2008) (14) explained that following a brain injury, the brain attempts to reduce the amount of metabolism taking place in an effort to protect damaged neurons. This effect is mediated by GABA and may spread to other un-effected areas of the brain. Zolpidem may work to reverse this dormancy effect(14). Zolpidem was administered using the same dosage and methods as outlined by Whyte and Meyers (2009). (3) Zolpidem 10 mg was administered in liquid form via the feeding tube followed by a flush of water (90 mls). In contrast to the approach of Whyte and Meyers (2009), (3) who instructed the research observer to interact freely with the patients involved, the team in this current case report carried out eight structured interdisciplinary multi-sensory hierarchical protocols over an eight week period. Each weekly session took place within 30–60 min of Zolpidem administration (see Appendix 1)
Premenstrual syndrome as a risk factor for relapse in GHB dependent patients: a case series
Published in Journal of Substance Use, 2020
Rouhollah Qurishi, Marieke Arts-De Jong, Victor J. A. Buwalda, Linda Hartman, Cornelis A. J. De Jong
An association between PMS and depressive disorders has been documented (Halbreich & Endicott, 1985). Recently, the growth hormone response to the GABA B receptor agonist baclofen was reported to increase during the luteal phase of the menstrual cycle of normal women (O’Keane & Dinan, 1994). As opposed to other neurotransmitters, GABA agonists up-regulate GABAergic receptors, and depressive analogs are combined with low GABA levels and down-regulated GABA B receptors (Lloyd, Zivkovic, Scatton, Morselli, & Bartholini, 1989). Hence, it could be predicted that a greater reaction to baclofen is associated with higher GABA levels. Therefore, it was suggested that plasma GABA levels would increase from the follicular to the luteal phase of a normal female’s cycle and that females with PMDD would have lower plasma GABA levels, especially during the dysphoric, late luteal phase (Halbreich et al., 1996).
Free latissimus dorsi flap for upper extremity reconstruction in a 9-month-old
Published in Case Reports in Plastic Surgery and Hand Surgery, 2021
Ryan D. Wagner, Jacqueline S. Yang, Brittany E. Bryant, William C. Pederson, Shayan A. Izaddoost
In 2016 and 2017, the FDA released drug safety communications warning that surgeries in children younger than 3 years involving multiple or lengthy exposures to general anesthesia and sedative drugs could affect brain development. Furthermore, these warnings suggested sedation over 3 hours could be linked to long-term behavioral or learning deficits [5,6]. These conclusions were based primarily on animal studies that found widespread neuronal death after hours of prolonged NMDA inhibitor anesthesia usage [7,8]. Subsequent studies have shown that GABA agonists can also negatively impact neurodevelopment [9]. While this data in mice, rats, and non-human primates presents significant concerns for the field of pediatric anesthesia and surgery, the implications of these neurotoxic effects have not yet been clearly translated into human metrics [10,11]. With this new data, reconstructive surgeons have to be extremely diligent when planning large reconstructive procedures in the young pediatric population and always weigh the risks and benefits of early intervention.
Related Knowledge Centers
- Action Potential
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