Editing Calcium channel blocker (section)

==Classes==

=== Dihydropyridine ===
[[File:Dipines.svg|thumb|right|class=skin-invert-image|General chemical structure of dihydropyridine calcium channel blockers (dipines)]]
Dihydropyridine (DHP) calcium channel blockers are derived from the molecule [[dihydropyridine]] and often used to reduce systemic vascular resistance and arterial pressure. Sometimes when they are used to treat [[angina pectoris|angina]], the vasodilation and hypotension can lead to reflex [[tachycardia]], which can be detrimental for patients with [[ischemic]] symptoms because of the resulting increase in [[myocardial]] oxygen demand. Dihydropyridine calcium channel blockers can worsen [[proteinuria]] in patients with [[nephropathy]].<ref>{{Cite journal |vauthors=Remuzzi G, Scheppati A, Ruggenenti P |year=2002 |title=Clinical Practice. Nephropathy in Patients with Type 2 Diabetes |journal=New England Journal of Medicine |volume=346 |issue=15 |pages=1145–51 |doi=10.1056/NEJMcp011773 |pmid=11948275}}</ref>

This CCB class is easily identified by the suffix "-dipine".
* [[Amlodipine]] (Norvasc)
* [[Aranidipine]] (Sapresta)
* [[Azelnidipine]] (Calblock)
* [[Barnidipine]] (HypoCa)
* [[Benidipine]] (Coniel)
* [[Cilnidipine]] (Atelec, Cinalong, Siscard) Not available in US
* [[Clevidipine]] (Cleviprex)
* [[Efonidipine]] (Landel)
* [[Felodipine]] (Plendil)
* [[Isradipine]] (DynaCirc, Prescal)
* [[Lacidipine]] (Motens, Lacipil)
* [[Lercanidipine]] (Zanidip)
* [[Manidipine]] (Calslot, Madipine)
* [[Nicardipine]] (Cardene, Carden SR)
* [[Nifedipine]] (Procardia, Adalat)
* [[Nilvadipine]] (Nivadil)
* [[Nimodipine]] (Nimotop) This substance can pass the [[Blood brain barrier|blood-brain barrier]] and is used to prevent [[cerebral vasospasm]].
* [[Nisoldipine]] (Baymycard, Sular, Syscor)
* [[Nitrendipine]] (Cardif, Nitrepin, Baylotensin)
* [[Pranidipine]] (Acalas)

===Non-dihydropyridine===

==== Phenylalkylamine ====
[[Image:Verapamil skeletal.svg|thumb|class=skin-invert-image|[[Skeletal formula]] of [[verapamil]]]]

Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina, where tachycardia can be the most significant contributor to the heart's need for oxygen. Therefore, as vasodilation is minimal with the phenylalkylamines, the major mechanism of action is causing negative inotropy. Phenylalkylamines are thought to access calcium channels from the intracellular side, although the evidence is somewhat mixed.<ref>{{Cite journal |last=Hockerman, G.H. |last2=Peterson, B.Z. |last3=Johnson, B.D. |last4=Catterall, W.A. |year=1997 |title=Molecular Determinants of Drug Binding and Action on L-Type Calcium Channels |journal=Annual Review of Pharmacology and Toxicology |volume=37 |pages=361–96 |doi=10.1146/annurev.pharmtox.37.1.361 |pmid=9131258 |s2cid=16275155}}</ref>
* [[Fendiline]]
* [[Gallopamil]]
* [[Verapamil]] (Calan, Isoptin)

==== Benzothiazepine ====
[[Image:Diltiazem Structural Formulae V.1.svg|thumb|class=skin-invert-image|[[Structural formula]] of [[diltiazem]]]]

Benzothiazepine calcium channel blockers belong to the [[Thiazepine|benzothiazepine]] class of compounds and are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines.{{cn|date=May 2025}}
* [[Diltiazem]] (Cardizem) (also used experimentally to prevent migraine){{citation needed|date=March 2022}}

====Nonselective====
While most of the agents listed above are relatively selective, there are additional agents that are considered nonselective. These include [[mibefradil]], [[bepridil]], [[flunarizine]] ([[blood–brain barrier|BBB]] crossing), [[fluspirilene]] ([[blood–brain barrier|BBB]] crossing),<ref name="pmid7565636">{{Cite journal |vauthors=Bezprozvanny I, Tsien RW |year=1995 |title=Voltage-Dependent Blockade of Diverse Types of Voltage-Gated Ca<sup>2+</sup> Channels Expressed in ''Xenopus'' Oocytes by the Ca<sup>2+</sup> Channel Antagonist Mibefradil (Ro 40-5967) |url=http://molpharm.aspetjournals.org/content/48/3/540.abstract |journal=Molecular Pharmacology |volume=48 |issue=3 |pages=540–49 |doi=10.1016/S0026-895X(25)10504-X |pmid=7565636}}</ref> and [[fendiline]].<ref name="pmid1755331">{{Cite journal |vauthors=Scultéty S, Tamáskovits E |year=1991 |title=Effect of Ca<sup>2+</sup> Antagonists on Isolated Rabbit Detrusor Muscle |journal=Acta Physiologica Hungarica |volume=77 |issue=3–4 |pages=269–78 |pmid=1755331}}</ref>

====Others====
[[Gabapentinoid]]s, such as [[gabapentin]] and [[pregabalin]], bind selectively to the [[CACNA2D1|α<sub>2</sub>δ protein]] that was first described as an integral part of [[voltage-gated calcium channel]]s. These drugs do not directly block calcium channels<ref>{{Cite journal |last=Taylor |first=Charles P. |last2=Harris |first2=Eric W. |date=2020 |title=Analgesia with Gabapentin and Pregabalin May Involve N-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins |url=https://jpet.aspetjournals.org/content/374/1/161 |journal=Journal of Pharmacology and Experimental Therapeutics |language=en |volume=374 |issue=1 |pages=161–174 |doi=10.1124/jpet.120.266056 |issn=0022-3565 |pmid=32321743|url-access=subscription }}</ref><ref>{{Cite journal |last=Varadi |first=Gyula |date=2024 |title=Mechanism of Analgesia by Gabapentinoid Drugs: Involvement of Modulation of Synaptogenesis and Trafficking of Glutamate-Gated Ion Channels |journal=Journal of Pharmacology and Experimental Therapeutics |language=en |volume=388 |issue=1 |pages=121–133 |doi=10.1124/jpet.123.001669 |issn=0022-3565 |pmid=37918854 |doi-access=free}}</ref> but can alter the transport of functional calcium channels to the cell membrane and they also reduce the release of certain excitatory neurotransmitters. They are used primarily to treat [[epilepsy]] and [[neuropathic pain]].<ref>{{Cite journal |last=Zamponi |first=GW |last2=Striessnig |first2=J |last3=Koschak |first3=A |last4=Dolphin |first4=AC |date=October 2015 |title=The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential. |journal=Pharmacological Reviews |volume=67 |issue=4 |pages=821–70 |doi=10.1124/pr.114.009654 |pmc=4630564 |pmid=26362469}}</ref> More recently, the α<sub>2</sub>δ-1 protein has been found to bind directly and to interact with certain glutamate receptors and to the interstitial protein thombospondin, independently from their action at calcium channels.{{cn|date=May 2025}}

[[Ziconotide]], a [[peptide]] compound derived from the omega-[[conotoxin]], is a selective [[N-type calcium channel]] blocker that has potent [[analgesic]] properties that are equivalent to approximate 1,000 times that of [[morphine]]. It must be delivered via the intrathecal (directly into the cerebrospinal fluid) route via an intrathecal infusion pump.<ref name="McDowell 2016">{{Cite journal |last=McDowell |first=GC |last2=Pope |first2=JE |date=July 2016 |title=Intrathecal Ziconotide: Dosing and Administration Strategies in Patients With Refractory Chronic Pain |journal=Neuromodulation |volume=19 |issue=5 |pages=522–32 |doi=10.1111/ner.12392 |pmc=5067570 |pmid=26856969}}</ref>

Naturally occurring compounds and elements such as [[magnesium]] have also been shown to act as calcium channel blockers when administered orally.<ref>{{Cite journal |last=Houston |first=M. |year=2011 |title=The role of magnesium in hypertension and cardiovascular disease |journal=Journal of Clinical Hypertension (Greenwich, Conn.) |volume=13 |issue=11 |pages=843–847 |doi=10.1111/j.1751-7176.2011.00538.x |pmc=8108907 |pmid=22051430}}</ref>