Applied physiology: neuropathic pain
Peter R Wilson, Paul J Watson, Jennifer A Haythornthwaite, Troels S Jensen in Clinical Pain Management, 2008
A calcium channel subunit that has received much attention of late is the α2δ-1 subunit. This subunit is up-regulated in rat DRG neurons, on central afferents terminals and on neurons within the spinal dorsal horn following nerve injury (Figure 1.5).74,75 This is correlated with pain behavior following peripheral nerve injury suggesting that α2δ-1 may contribute to neuroplasticity in neuropathic pain. In support of this, transgenic mice that constitutively overexpress α2δ-1 in neuronal tissues demonstrate pain behavior and exaggerated and prolonged dorsal horn neuronal responses to peripheral mechanical and thermal stimulation.76 Furthermore, the α2δ-1 subunit is thought to be the site of action of gabapentin77,78 and pregabalin,79 which are effective in relieving signs of hypersensitivity in animal models80 and neuropathic pain in man.64,81
Preventive analgesia and beyond: current status, evidence, and future directions
Pamela E Macintyre, Suellen M Walker, David J Rowbotham in Clinical Pain Management, 2008
Gabapentin is a structural analogue of γ-aminobutyric acid (GABA) and was introduced into clinical practice as an anticonvulsant drug. Its main binding site is believed to be the alpha-2-delta subunit of voltage-dependent calcium channels, but its full mechanism of action is not well understood.106 Other postulated mechanisms of action have been proposed, such as selectively activating GABAB receptors, selectively enhancing the NMDA current at GABAergic interneurons, or blocking α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated transmission in the spinal cord.106 More recently, gabapentin has been shown to increase tonic inhibitory conductance in mammalian hippocampal neurons.107 Thus, a combination of peripheral and central effects likely mediate the clinical effects of this drug.
Embryo Transfer
Arianna D'Angelo, Nazar N. Amso in Ultrasound in Assisted Reproduction and Early Pregnancy, 2020
Oxytocin receptor antagonists that act by antagonizing naturally synthesized oxytocin as well as vasopressin at their receptors in the myometrium, promoting uterine relaxation [22]. Prostaglandin synthetase (cyclooxygenase) inhibitors that reduce prostaglandins (PGF2α and PGE2) and thromboxane A2, which are involved in myometrial contractions in nonpregnant and pregnant uteri [23–25].Nitric oxide that relaxes smooth muscle, helping with vasodilatation and possibly helping by inducing relaxation of the smooth muscles of the myometrium as shown in pregnancy [26,27].Beta-adrenergic receptor agonists that promote the relaxation of the smooth muscle in cases of preterm labor [28] and in the nonpregnant uterus [29].Anticholinergic agents that cause relaxation of the myometrial smooth muscles [30,31].Calcium channel blockers that inhibit the influx of calcium ions through the cell membranes of smooth muscle, inhibiting contractions. Their use has been reported for tocolysis [32].
The effect of the calcium channel blocker nimodipine on hippocampal BDNF/Ach levels in rats with experimental cognitive impairment
Published in Neurological Research, 2023
Atilla Topcu, Sinan Saral, Aykut Ozturk, Ozlem Saral, Ali Koray Kaya
Calcium channels are responsible for numerous functions in the central nervous system. A previous study showed that calcium channels mediate experimentally induced neurodegeneration [24]. Nimodipine is a dihydropyridine-derivative calcium channel blocker used in aneurysmal subarachnoid hemorrhage due to the vasoselectivity it exhibits in the cerebral vessels [25,26]. Previous experimental studies have confirmed the neuroprotective effects of nimodipine [27,28]. Koskimaki et al. revealed that nimodipine is capable of somehow activating synaptic plasticity in experimentally induced brain trauma [29]. That study revealed the effect of nimodipine on the BDNF-TrkB signaling pathway. It may thus be concluded that nimodipine administration may be beneficial in reversing impaired cognitive function through its regulatory effects on the BDNF-TrkB and CREB signaling pathways [30].
Non-opioid antinociceptive drugs : risk of respiratory depression and death related to concomitant use of gabapentinoids in addition to opioids
Published in Expert Opinion on Drug Safety, 2023
Marine Tambon, Berenice Montarnal, Marianne Lepetit, Maryse Lapeyre-Mestre
These agents are chemically closed to GABA (gamma-amino-butyric-acid) but are not directly acting on GABA receptors. They are ligands of the α2δ calcium channel subunit, an auxiliary protein connected to the main α1 subunit of voltage-dependent calcium channels. Gabapentinoids reduce the activation of the channels by the α2δ subunit and then decrease signaling, leading to neurotransmitters release. Initially, gabapentin and pregabalin were presented with a low potential of misuse and abuse, and the risk of respiratory depression has not been initially reported, with data from safety pharmacology indicating that pulmonary function was unaffected. Clinical experience and experimental studies now indicate that gabapentin and pregabalin may by themselves induce respiratory depression [7–10].
Solanaceae glycoalkaloids: α-solanine and α-chaconine modify the cardioinhibitory activity of verapamil
Published in Pharmaceutical Biology, 2022
Szymon Chowański, Magdalena Winkiel, Monika Szymczak-Cendlak, Paweł Marciniak, Dominika Mańczak, Karolina Walkowiak-Nowicka, Marta Spochacz, Sabino A. Bufo, Laura Scrano, Zbigniew Adamski
Calcium ions play a crucial role in muscle contractions, and therefore, L-type calcium channels that move Ca2+ ions inward and trigger calcium release from the sarcoplasmic reticulum by activating the ryanodine receptor 2 (Striessnig et al. 2014) are just as important. Dysregulation of L-type Ca2+ channels is the basis of numerous cardiac disorders; therefore, they are also a common target in various therapies for cardiovascular diseases. L-type Ca2+ channel blockers, such as verapamil, are commonly used to treat hypertension, myocardial ischaemia, and arrhythmias (Limpitikul et al. 2018). The so-called α1 subunit forms the core of voltage-sensitive L-type Ca2+ channels. It associates with other subunits (β, α2δ, γ) to form heterooligomeric complexes. The β and α2/δ subunits are tightly but not covalently bound to the α1 subunit and modulate the biophysical properties and trafficking of the α1 subunit to the membrane (Bodi et al. 2005). The presence of L-type Ca2+ channels were also confirmed in the myocardium of Drosophila melanogaster (Limpitikul et al. 2018) and Musca domestica (Grabner et al. 1994). This tissue builds the dorsal vessel of the insect, traditionally called the heart. Even if not anatomically, the insect heart functionally and developmentally resembles the embryonic vertebrate heart. Thus, it offers an attractive alternative for studies conducted on mammals. Furthermore, many analyses can be performed in vivo without the need to sacrifice the test animal (Limpitikul et al. 2018).
Related Knowledge Centers
- Calcium
- Calcium Channel Blocker
- Depolarization
- Hypertension
- Epilepsy
- Ion Channel
- Voltage-Gated Calcium Channel
- Vasoconstriction
- P2X Purinoreceptor