Table 2.

Functional roles of clinically available/potential modulators of K_Ca channels.

Target	Drug	Reported effects	Comments	References
SK	1-EBIO	-Positive effects on cerebral ischemia animal models	-SK activator	Allen et al., 2011; Lappin et al., 2005; Anderson et al., 2006; Oliveira et al., 2010
		-Reduces epileptiform activity in an acute model of epilepsy
	NS309	Positive effects on DA neurons function related to Parkinson’s disease	-SK activator	Ji and Shepard, 2006; Dolga et al., 2014
	Chlorzoxazone	Improves motor-coordination and other symptoms of episodic ataxia type-2	-SK activator	Alvina and Khodakhah, 2010
			-FDA-approved treatment for spasticity
	Riluzole	-Positive effects in arthritic pain model	-SK activator	Ristori et al., 2010; Thompson et al., 2015
		-Improves ataxia-related symptoms in human patients	-FDA-approved treatment for ALS
	DCEBIO	Reduces recall of extinction memory in rats	SK activator	Criado-Marrero et al., 2014
	Apamin	-Improves Parkinson’s disease symptoms in vitro and in vivo	SK inhibitor	Deschaux et al., 1997; Inan et al., 2000; Stackman et al., 2002; Mpari et al., 2005; Doo et al., 2010; Yang E.J. et al., 2010; Kim et al., 2011; Alvarez-Fischer et al., 2013; Criado-Marrero et al., 2014
		-Positive effects on various memory deficits and spatial learning
IK	TRAM-34	-Positive effects in AD, ischemic stroke and multiple sclerosis mouse models	IK inhibitor	Reich et al., 2005; Chen Y.J. et al., 2016; Yi et al., 2016; Lu et al., 2017
		-Increases formalin-induced nociceptive behavior
	Senicapoc	-Positive effects in sickled cell anemia disease (SAD)∗	-IK inhibitor	Wulff and Castle, 2010; Staal et al., 2017
		-Reversed tactile allodynia in rats with peripheral nerve injury	-Phase 3 clinical trials for SAD
			-Phase 2 clinical trials for asthma
BK	Isoprimaric acid (ISO)	-Improves cognitive defects in AD animal models	-BK activator	Wang L. et al., 2015
	GoSlo	-Inhibits spontaneous contractions in both bladder and corpus cavernosum smooth muscle tissues.	-BK activator	Large et al., 2015; Hannigan et al., 2017
	Andolast	Positive effects on asthma treatment	-BK activator	Malerba et al., 2015
			-Currently in late stage of phase 3 clinical trials for asthma
	BMS204352	-Positive effects on FXS animal models	-BK and Kv7 activator	Jensen, 2002; Brown and Passmore, 2009; Hebert et al., 2014; Zaman et al., 2017; Carreno-Munoz et al., 2018
		-Enhances short-term habituation	-Phase 3 clinical trials for treatment of acute ischemic stroke∗
		-Positive effects on spontaneous hypertensive rats model∗
	Zonisamide	-Positive effects on a wide range of epilepsies and neuropsychiatric disorders	-BK activator, Na+ and Ca2+ channel modulator	Biton, 2007; Huang et al., 2007
			-Antiepileptic drug used clinically
	Iberiotoxin (IbTX)	Beneficial effects in rheumatoid arthritis animal models	selective BKαβ1-3 blocker	Tanner et al., 2018

This table includes additional information, not detailed in the main text, about K_Ca modulators reported in the literature to treat diverse pathological conditions.