Editing Calcium channel blocker (section)

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[[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>