China
Africa
Explore chapters and articles related to this topic
Pharmacotherapy of Neurochemical Imbalances
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Rupali Patil, Aman Upaganlawar, Suvarna Ingale
Like with other neurotransmitters, glycine is released into the synaptic cleft on the receipt of an action potential in the presynaptic glycinergic neuron which promotes a cascade of reaction leading to vesicular fusion and diffuses and binds with its receptors located on the post-synaptic cell membrane (Rang et al., 2011).
Kindling
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
An interesting potentiating interaction between orally administered glycine and diazepam has been reported by Peterson in kindled rats, which suggests that a glycinergic action may exist in addition to the GABAergic effect of diazepam.153 A method for studying the time course of drug action in kindled seizures has been reported using diazepam as a representative antiepileptic drug.154 Intrauterine exposure of rats to diazepam on gestation days 14 to 20 demonstrated that a high dose (5 mg/kg) produced increased susceptibility to PTZ-kindled seizures in 60 day old animals155 by some unexplained means. Morimoto and Goddard156 studied the rhythmic spiking that developed in the amygdala, hippocampus, and piriform cortex during kindling and noted that the increase in amplitude was sensitive to diazepam, but not to GABAergic, monoaminergic, or cholinergic manipulations. This suggests that additional attention must be devoted to benzodiazepine binding sites within the limbic system if the rhythmic spiking is indeed specifically associated with the kindling process as these investigators have suggested.156
Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
At the present time, there are no clinically available drugs whose mechanism of action is mediated through glycinergic neurotransmission. However, there is an experimental drug called milacemide that is believed to increase glycine levels in the brain and has been shown to have anticonvulsant effects in experimental animals. Glycinergic neurons in the brain stem and spinal cord have been shown to play a role in suppressing pain, and there is now much interest in developing inhibitors of the glycine transporter-2 (GlyT2) to treat chronic pain.167 At the present time, we have no clinically useful antiepileptic drugs that act on glycine neurotransmission.1
Emerging drugs for the treatment of postsurgical pain
Published in Expert Opinion on Emerging Drugs, 2021
Esra Kutlu Yalcin, Jorge Araujo-Duran, Alparslan Turan
Understanding the different molecular pathways associated with pain has led to the discovery of new potential targets. For instance, the glycinergic pathway localized in specific brain regions and spinal cord has been shown to play an important role in the regulation of pain signal transduction, specifically through the Glycine transporter (GlyT) 1, which is present in glial cells, and GlyT2, which is located in neurons [38]. The transporters modulate glycinergic neurotransmission by clearing synaptically released glycine or supplying glycine to the neurons, modifying pain signal transmission in the spinal cord [38]. Previous preclinical studies demonstrated that blocking GlyT1 and GlyT2 produced a profound anti-allodynic effect in neuropathic pain models, mainly through the stimulation of the glycine receptor α3 [38]. This suggested the GlyTs as targets to develop medications for neuropathic and postoperative pain. Another pathway involves 5HT2A, a subtype of the 5HT2 serotonin receptor widely expressed in peripheral sensory neurons and responds to serotonin released during inflammation or nociceptive stimulation. It is also expressed in the midbrain neuron terminations and is involved in the amplification of pain signals in the spinal dorsal horn [39]. Different preclinical pain models led to the finding of the synergistic action between GlyT2 and 5HT2A inhibition as a potential drug to treat postoperative pain.
A Pilot Randomized, Placebo-Controlled Trial of Glycine for Treatment of Schizophrenia and Alcohol Dependence
Published in Journal of Dual Diagnosis, 2019
Jane Serrita, Elizabeth Ralevski, Gihyun Yoon, Ismene Petrakis
In addition to the beneficial effects for treating schizophrenia, glycine may have therapeutic potential for alcohol use disorder. In preclinical studies, the enhancement of glycinergic activity reduces alcohol consumption, relapse-like drinking behavior, and alcohol preference (Lido, Marston, Ericson, & Soderpalm, 2012; Molander, Lido, Lof, Ericson, & Soderpalm, 2006; Vengeliene, Leonardi-Essmann, Sommer, Marston, & Spanagel, 2010). The activation of glycine receptors in the nucleus accumbens by either glycine or glycine transport-inhibitors can reduce alcohol intake (Lido, Ericson, Marston, & Soderpalm, 2011; Soderpalm & Ericson, 2013; Soderpalm, Lido, & Ericson, 2017). Glycine has been safely used in human studies and in patients with alcohol use disorders (Krystal et al., 2011). Its use in alcohol use disorders is complicated, however; when given as an adjunct with D-cycloserine in alcohol-dependent individuals glycine increased the subjective ethanol-like effects produced by D-cycloserine. Those results suggest that increases in brain glycine levels might not be beneficial in alcohol use disorders. In a sample of 40 patients, glycine was effective for treating acute alcohol hallucinosis (Aliyev & Aliyev, 2005).
Glycine transporter-1 inhibitors: a patent review (2011–2016)
Published in Expert Opinion on Therapeutic Patents, 2018
Morphological mapping studies show diffuse GlyT-1 expression within the CNS with highest levels of distribution found in caudal areas (cerebellum, brain stem, and spinal cord) and lower levels in the forebrain (hippocampus, striatum, and prefrontal cortex (PFC)) [51–60]. Within the hindbrain, the transporter is largely localized on glial cells where it serves to termination of inhibitory glycinergic neurotransmission by clearing synaptic glycine from the GlyRs [61]. Therefore, inhibition of GlyT-1 in these regions results in increased EL glycine concentrations and enhanced inhibitory glycinergic neurotransmission. Within the forebrain, GlyT-1 is expressed on glial cells as well as on pre- and postsynaptic glutamatergic neurons where it is highly co-localized with NMDA receptors. The transporter carefully maintains synaptic glycine concentrations below saturation levels at the glycine-B binding site [62–64]. Thus, inhibition of GlyT-1 may also lead to increased NR1 glycine-B site occupancy and enhanced NMDA receptor function. Thus, GlyT-1 plays a critical role in tightly controlling homeostatic EL glycine concentrations throughout the CNS, thus serving as key modulatory component of both inhibitory and excitatory neurotransmission. Last, GlyT-1 is also expressed within mammalian and nonmammalian retinae, where it is co-localized expressed on amacrinal cells and Muller glial cells [65,66].