China
Africa
Explore chapters and articles related to this topic
Blood Flow and Its Modulation in Malignant Tumors
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
This class of drugs, which specifically block the entry of calcium into cells,89 has been used in the treatment of angina, hypertension, and other cardiovascular disorders.90 They may be divided into several categories based on their chemical structure91 and their preferential site of action. The benzothiapine diltiazem is rather specific in its action, targeting mainly coronary vessels; the 1,4-dihydropyridine nifedipine causes relaxation of the larger blood vessels, whereas the diphenylpiperizine flunarizine acts more peripherally. The phenylalkylamine verapamil is the least specific of these agents, acting on cardiac muscle, coronary vessels, and other large vessels.
Hypertension
Published in Nicholas Green, Steven Gaydos, Hutchison Ewan, Edward Nicol, Handbook of Aviation and Space Medicine, 2019
Nicholas Green, Steven Gaydos, Hutchison Ewan, Edward Nicol
Especially useful in aircrew with diabetes or hyperlipidaemia, as exert no effect on these metabolic pathways (do not require routine screening of renal or liver function). Dihydropyridine CCB (such as amlodipine) are acceptable in aircrew, both civil and military.Phenylalkylamine agents (such as verapamil) and benzothiazepine agents (such as diltiazem) have both negative inotropic and chronotropic effects and should be used with caution in aircrew; restricted to aircrew of non-high-performance aircraft only.
Migraine Medications
Published in Gary W. Jay, Clinician’s Guide to Chronic Headache and Facial Pain, 2016
Verapamil, a phenylalkylamine, has been evaluated for prophylactic treatment of migraine. Three double-blind, placebo-controlled trials were done but they were very small: with 10 of 12 patients, 8 of 14 patients, and 20 of 23 patients showing improvement, and the 320 mg/day dosage better than the 240 mg/day dosage (95). On the other hand, multiple other authors indicated that verapamil may be useful in migraine prophylaxis (96-98).
Etripamil nasal spray: an investigational agent for the rapid termination of paroxysmal supraventricular tachycardia (SVT)
Published in Expert Opinion on Investigational Drugs, 2020
Anthony H. Kashou, Peter A. Noseworthy
Etripamil nasal spray (Milestone Pharmaceuticals, Montreal St.-Laurent, Quebec, Canada) is a short-acting, phenylalkylamine class, non-dihydropyridine L-type calcium-channel blocker. It acts to slow atrioventricular (AV) nodal conduction and prolong AV nodal refractory periods by inhibiting calcium ion influx through the calcium slow channels in AV nodal cells. More specifically, voltage mapping has shown etripamil selectively affects the slow pathway bridge with gradual voltage recovery in this area and slow recovery of AV nodal conduction after several minutes [9]. Serum esterases metabolize the drug into an inactive carboxylic acid. The intranasal formulation has a high potency with a time to maximum plasma concentration of about 8 min and a short mean first half-life of about 20 min. The rapid onset and offset of action allows for immediate use and avoids potential complications of long-acting therapies, respectively.
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
Verapamil is a prototypical phenylalkylamine and was the first calcium channel blocker used clinically. It tonically blocks L-type channels with micromolar affinity (DrugBank 2021). Based on the relative specificity of the L-type Ca2+ channel antagonist, verapamil blocks conduction, especially in sinus nodal-like cells. Consequently, it changes the spiking rhythmicity and electrical propagation, e.g., in embryonic stem cell-derived cardiomyocytes (Reppel et al. 2007), and thus, decreases myocardial contractility with negative inotropic and chronotropic effects (Kurola et al. 2010). Due to its properties, it is commonly used as an antiarrhythmic and vasodilating medication.
Gene knockdown of HCN2 ion channels in the ventral tegmental area reduces ethanol consumption in alcohol preferring rats
Published in The American Journal of Drug and Alcohol Abuse, 2022
Catalina Salinas-Luypaert, Felipe Sáez-Cortez, María Elena Quintanilla, Mario Herrera-Marschitz, Mario Rivera-Meza
A limited number of studies have explored the role of nonselective HCN blockers on ethanol effects. An early work by Messiha et al. (53) demonstrated that the systemic administration of cesium chloride to rats, a known blocker of HCN channels, resulted in a moderate reduction of voluntary ethanol intake without affecting the ethanol metabolizing enzymes in the liver. Ex-vivo studies of brain slices provide further evidence regarding the effect of HCN chemical blockers on the excitation of dopaminergic neurons elicited by ethanol. A study from Okamoto et al. (16) in midbrain slices from C57BL/6 J mice showed that the HCN blocker ZD7288 was able to suppress the stimulatory effects of ethanol on the firing rate of VTA dopamine neurons. In contrast, studies performed in brain slices from DBA/2 J mice and Fischer-344 rats have demonstrated that the incubation with cesium chloride or ZD7288 did not prevent the excitation of dopaminergic neurons elicited by ethanol (17,54). The development of pharmacological agents aimed at selectively modifying the activity of different isoforms of HCN ion channels is limited. Ivabradine is the only nonselective HCN blocker approved for clinical use as a heart rate lowering agent. Other nonselective blockers of HCN channels, such as ZD7288, zatebradine, and cilobradine display similar pharmacological properties. In vitro studies have allowed to identify differences in the amino acid composition at the binding region of HCN1, HCN2, and HCN4 isoforms, leading to the development of new blockers with some selectivity for the different isoforms of HCN ion channels (55). Regarding the HCN2 variant, Melchiorre et al. (56) described the synthesis of MEL55A, a phenylalkylamine-derived compound, which is able to reduce the activity of HCN channels by 50% at low concentrations (2 µM), showing an affinity 10-fold higher for HCN2 than for HCN4. A recent study also reported the development of a new series of alkanol amine derivatives with blocking activity on HCN channels. One of these assayed compounds, named 4e, showed in electrophysiological assays an IC50 of 2.9 µM for the HCN2 channel, which is 5- and 2-fold lower compared to the IC50 observed for HCN1 and HCN4 channels, respectively (57). There are no reports of studies aimed at studying the effectiveness of these selective blockers of HCN2 to reduce the consumption of ethanol.