Nefopam—penghambat reuptakepengambilan monoaminekembali monoamin, serta modulator saluran kalsium dan natrium—juga disetujui untuk pengobatan nyeri sedang hingga berat di beberapa negara.[33]<ref>{{cite journal | vauthors = Girard P, Chauvin M, Verleye M | title = Nefopam analgesia and its role in multimodal analgesia: A review of preclinical and clinical studies | journal = Clinical and Experimental Pharmacology & Physiology | volume = 43 | issue = 1 | pages = 3–12 | date = January 2016 | pmid = 26475417 | doi = 10.1111/1440-1681.12506 | doi-access = free }}</ref>
FlupirtineFlupirtin adalah pembuka saluran K<sup>+</sup> yang bekerja secara terpusat dengan sifat antagonis NMDA yang lemah.[34]<ref>{{cite journal | vauthors = Kornhuber J, Bleich S, Wiltfang J, Maler M, Parsons CG | title = Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. Rapid communication | journal = Journal of Neural Transmission | volume = 106 | issue = 9–10 | pages = 857–67 | year = 1999 | pmid = 10599868 | doi = 10.1007/s007020050206 | s2cid = 11636934 }}</ref> Obat Itutersebut digunakan di Eropa untuk nyeri sedang hingga kuat, serta sifat mengobati [[migrain]] dan pelemas [[otot]]. Ia tidak memiliki sifat [[antikolinergik]] yang signifikan, dan diyakini tidak memiliki aktivitas apa pun pada reseptor [[dopamin]], [[serotonin]], atau [[histamin]]. Obat ini tidak membuat ketagihan, dan toleransi biasanya tidak berkembang.[35]<ref>{{cite journal | vauthors = Klawe C, Maschke M | title = Flupirtine: pharmacology and clinical applications of a nonopioid analgesic and potentially neuroprotective compound | journal = Expert Opinion on Pharmacotherapy | volume = 10 | issue = 9 | pages = 1495–500 | date = June 2009 | pmid = 19505216 | doi = 10.1517/14656560902988528 | s2cid = 11597721 }}</ref> Namun, toleransi dapat berkembang dalam beberapa kasus.[36]<ref>{{cite journal | vauthors = Stoessel C, Heberlein A, Hillemacher T, Bleich S, Kornhuber J | title = Positive reinforcing effects of flupirtine--two case reports | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 34 | issue = 6 | pages = 1120–1 | date = August 2010 | pmid = 20362025 | doi = 10.1016/j.pnpbp.2010.03.031 | s2cid = 19710997 }}</ref>
ZiconotideZikonotid, penghambat saluran kalsium berpintu tegangan tipe N yang kuat, diberikan secara intratekal untuk meredakan nyeri parah yang biasanya berhubungan dengan kanker.[37]<ref>{{cite journal | vauthors = Bäckryd E | title = Do the potential benefits outweigh the risks? An update on the use of ziconotide in clinical practice | journal = European Journal of Pain | volume = 22 | issue = 7 | pages = 1193–1202 | date = August 2018 | pmid = 29635804 | doi = 10.1002/ejp.1229 | url = http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-149838 | s2cid = 4710528 }}</ref>
