China
Africa
Explore chapters and articles related to this topic
Ethnomedicinal Plants of North Eastern Himalayan Region of India to Combat Hypertension
Published in Amit Baran Sharangi, K. V. Peter, Medicinal Plants, 2023
Pintubala Kshetri, K. Tamreihao, Subhra Saikat Roy, Thangjam Surchandra Singh, Susheel Kumar Sharma, Meraj Alam Ansari
R. serpentina is an evergreen shrub commonly known as Indian snakeroot widely distributed in the Indian subcontinent. It is a well-known folk medicine in India and is used in treating several important diseases. Clinical studies conducted by various researchers reveals that an active molecule “reserpine” extracted from the root is responsible for controlling the hypertensive activity of this plant (Wilkins and Judson, 1953). Reserpine, an alkaloid, is a drug used in treatment of hypertension. Sheldon and Kotte (1957) conducted 2-year double-blind study on the effect of reserpine on hypertensive patients, where they observed a significant reduction in BP of the patients. The mechanism of hypotensive activity is by inhibiting vesicular monoamine transporter (VMAT) 1 and 2 located at the neuroendocrine cells of the peripheral nervous system. The inhibition of VMAT’s blocked the L-type voltage-gated calcium channels and catecholamine secretion thereby lowering BP (Loby 2015; Mahata et al., 1996).
Homeostasis of Dopamine
Published in Nira Ben-Jonathan, Dopamine, 2020
Common to all monoaminergic neurotransmitters are reuptake mechanisms in which the released neurotransmitter is taken back into the secreting cell by membrane-embedded transporters. Reuptake fulfills two important functions: (1) guarding against neuronal overstimulation through the removal of the released messenger from the synaptic cleft, resulting in the rapid termination of its actions, and (2) enabling energy conservation by recycling and reutilizing existing molecules rather than producing energy-costly new transmitters [37]. Once the released molecule is brought back into the secreting cell, the next step is its repackaging into storage/secretory vesicles (Figure 1.6). Repackaging is accomplished by two vesicular monoamine transporters, VMAT1 and VMAT2, whose main roles are to (1) protect the transmitter from degradation by intracellular MAO, (2) maintain an adequate intraneuronal storage/secretory capacity to ensure prompt responses to subsequent stimuli, and (3) enable a regulated release of the neurotransmitter from storage vesicles rather than its unregulated release by diffusion [38].
Adrenergic Agonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
VMAT, a VNT, prevents leakage and deterioration of the neurotransmitters thereby maintaining a check in its concentration within the cytoplasm. These are of two types VMAT-1 and VMAT-2. VMAT-1 is located in the peripheral organs particularly the cells of the paracrine and endocrine glands whereas VMAT-2 is located in the vesicular transporter located in CNS, histaminergic cells of adrenal medulla, blood cells, and stomach (Mahata et al., 1993; Peter et al., 1995; Weihe et al., 1994; Erickson et al., 1996). Reserpine blocks both VMAT-1 as well as VMAT-2 leading to reduced uptake of dopamine as well as noradrenaline into the synaptic vesicles leading to its degradation by MAO thereby inhibiting adrenergic neurotransmission at the synapses. Apart from reserpine, tetrabenazine and methamphetamine also have competitive blocking action on VMAT-2, which is more sensitive compared to VMAT-1 (Erickson et al., 1996; Peter et al., 1994). The enhancement of storage of neurotransmitters like dopamine and noradrenaline can be a good remedy in the discipline of psychiatry and in behavioral, locomotory defective disorders like parkinsonism.
State-of-the-art pharmacological approaches to reduce chorea in Huntington’s disease
Published in Expert Opinion on Pharmacotherapy, 2021
Jessie S. Gibson, Daniel O. Claassen
VMAT-2 inhibitors deplete vesicular monoamines (e.g., dopamine), preventing their release from presynaptic vesicles [88]. This is thought to prevent dopamine from reaching upregulated D2 receptors, thereby reducing chorea. Tetrabenazine was the first VMAT-2 inhibitor to be approved, and it has been indicated for the treatment of HD chorea in the US since 2008 [88]. It is worth noting that reserpine was another early VMAT inhibitor which bound irreversibly to VMAT-1 and VMAT-2 receptors, causing long-lasting off-target effects such as hypotension and depression, and limiting its further use [18,89]. For years, tetrabenazine was the only medication approved by the FDA to treat HD chorea, and this is reflected in its continued frequent use by HD physicians [39]. Tetrabenazine is shown to be effective for reducing chorea severity in HD, though it is also associated with significant adverse effects including somnolence, akathisia, depression, and elevated risk for suicidality [18]. Tetrabenazine carries a black box warning for increased risk of suicidality in patients with HD, possibly due to off-target depletion of 5-HT and NE, and it is contraindicated in patients with uncontrolled depression [88]. However, some have argued that this in an over-cautious statement based on a small effect in a single trial, as follow-up analyses with larger samples have not found evidence of this risk [90,91]. Major metabolites of tetrabenazine have half-lives between 7 and 12 h, and it is recommended to be taken in divided doses up to three times per day [92].
Valbenazine as the first and only approved treatment for adults with tardive dyskinesia
Published in Expert Review of Clinical Pharmacology, 2018
Harini Sarva, Claire Henchcliffe
Vesicular monoamine transporters (VMATs) are 12-transmembrane proteins found throughout the body. They play a role in packaging monoamines into the presynaptic vesicles via active transport in the cytoplasm, using an ATP-ase-generated proton gradient [33]. VMAT2 is a potent transporter of monoamines (dopamine, norepinephrine, histamine, and serotonin) from the cytosol to synaptic vesicles in the brain and peripheral nervous system [33,34]. In the brain, VMAT2 can be found in the striatum, limbic region, and lateral striatum [33]. Thus, it is found in dopaminergic, histaminergic, serotonergic, and cholinergic neurons. Alterations in dopamine release presynaptically by these VMAT2 receptors can lead to postsynaptic dopamine receptor supersensitivity, which can play a role in the development of TD [35]. In contrast, the VMAT1 isoform is located primarily in the neuroendocrine cells and sympathetic ganglia of the peripheral nervous system [33,36].
Clinical development of valbenazine for tics associated with Tourette syndrome
Published in Expert Review of Neurotherapeutics, 2021
Robert H. Farber, Angel Angelov, Kristine Kim, Tara Carmack, Dao Thai-Cuarto, Eiry Roberts
Vesicular monoamine transporters (VMATs) are integral membrane proteins that play a critical role in packaging monoamines such as dopamine into presynaptic vesicles [22,23]. Two VMAT subtypes have been characterized: VMAT1, which is primarily expressed in neuroendocrine cells; and VMAT2, which is primarily expressed in the central nervous system [24]. Medications that inhibit VMAT2 (i.e. VMAT2 inhibitors) reduce the availability of dopamine in the synapse by modulating the presynaptic release. VMAT2 inhibitors have been used to treat hyperkinetic movement disorders such as chorea associated with Huntington’s disease and TD, and were thought to be a potential therapeutic option for the treatment of TS [25,26].