TABLE 1.
Putative medications are not limited to those listed above.
| Putative medications | Likely mechanism | Current use of medications |
|---|---|---|
| Predicted to decrease CAMK2 activity | ||
| Angiotensin/aldosterone inhibitors | Predicted to decrease CAMK2 activity by ↓ROS (Erickson 2014) | Hypertension |
| Anti-oxidant Riboflavin | Predicted to decrease CAMK2 activity by ↓ROS | Riboflavin: Headache prophylaxis |
| Baclofen | Predicted to decrease CAMK2 activity by Ⓖ↑GABA-BR inhibition (Evenseth et al., 2020) | Spasticity |
| Benzodiazepines | Predicted to decrease CAMK2 activity by Ⓖ↑GABA-AR inhibition (Sills and Rogawski, 2020) | Anxiety, epilepsy |
| Calcium channel blockers Dihydropyridine and non-dihydropyridine | Predicted to decrease CAMK2 activity by Ⓕ↓L-, T- TypeCa++ influx (Zamponi, 2015) | hypertension, tachycardia, headache prophylaxis |
| Coenzyme Q | Predicted to decrease CAMK2 activity by ↓cytosolic Ca++ in HepG2 cells in vivo (Xu et al., 2017) | supplement,headache prophylaxis |
| ↓ROS shown in other settings (Xu et al., 2017) | ||
| Cox-2 inhibitors | Predicted to decrease CAMK2 activity by ↓NOS ( ↑NOS shown to increase CAMK2ɑ expression (Varga et al., 2009; Coultrap and Bayer 2014) | Pain relief |
| Curcurmin | Predicted to decrease CAMK2 activity by ↓Ca++ dependent and independent CAMK2A phosphorylation (Mayadevi et al., 2012) | Supplement |
| ↓ unclear mechanism (Hu et al., 2015) | ||
| Dantrolene | Predicted to decrease CAMK2 activity (in muscle) by ↓RyR1 CICR (Zhao et al., 2001) | Malignant hyperthermia |
| ↓RyR3 CICR (Zhao et al., 2001) | ||
| Ethosuximide | Predicted to decrease CAMK2 activity by Ⓕ↓T- Type Ca++ | Epilepsy |
| Influx (Zamponi, 2015) | ||
| Ketamine | Predicted to decrease CAMK2 activity by Ⓙ↓NMDA Ca++ influx (Cui et al., 2009) | Anesthesia |
| Lamotrigine | Predicted to decrease CAMK2 activity by Ⓕ↓P/Q-, N-, R- Type Ca++ influx (Zamponi, 2015) | Epilepsy, mood disorders |
| ↓Presynaptic glutamine release (Deutschenbaur et al., 2016) | ||
| Lithium | Predicted to decrease CAMK2 activity by Ⓙ↓NMDA Ca++ influx (Nonaka, Hough, and Chuang 1998; Celano et al., 2003) | Mood disorders |
| ↓presynaptic CAMK2A phosphorylation by unknown mechanism (Nonaka et al., 1998; Celano et al., 2003) | ||
| Levetiracetam | Predicted to decrease CAMK2 activity by Ⓕ↓P/Q-, N- Type Ca++ influx (Dubovsky et al., 2015; Zamponi 2015) | Epilepsy |
| Ⓑ↓IP3 CICR (Nagarkatti et al., 2008; Zamponi, 2015) | ||
| Ⓓ↓AMPA receptor activation (Sills and Rogawski, 2020) | ||
| ↓RyR2 CICR (Nagarkatti et al., 2008; Zamponi, 2015) | ||
| Lubeluzole | Predicted to decrease CAMK2 activity by ↓Ca/CaM activity (Bruno et al., 2016) | Chemo-sensitization |
| Magnesium | Predicted to decrease CAMK2 activity by ↓Direct Ca++ antagonism | Supplement |
| Melatonin | Predicted to decrease CAMK2 activity by ↓Ca/CaM activity (Benítez-King et al., 1996) | Supplement |
| Perampanel | Predicted to decrease CAMK2 activity by Ⓓ↓AMPA receptor activation (Sills and Rogawski, 2020) | Epilepsy |
| Propofol | Predicted to decrease CAMK2 activity by Ⓙ↓NMDA Ca++ channel influx (Cui et al., 2009) | Anesthesia |
| Ⓖ↑GABA-AR inhibition (Cui et al., 2009) | ||
| Sodium Oxybate | Predicted to decrease CAMK2 activity by ↓inhibits CAMK2A holoenzyme (Leurs et al., 2021) | Narcolepsy |
| Topiramate | Predicted to decrease CAMK2 activity by Ⓕ↓R Type Ca++ influx (Zamponi 2015) | Epilepsy, mood disorders, headache prophylaxis |
| Ⓖ↑GABA-AR inhibition (Sills and Rogawski, 2020) | ||
| Valproic Acid | Predicted to decrease CAMK2 activity by Ⓕ↓T Type Ca++ influx (Zamponi 2015) | Epilepsy, mood disorders |
| Zonisamide | Predicted to decrease CAMK2 activity by Ⓕ↓T Type Ca++ influx (Zamponi 2015) | Epilepsy |
| Predicted to increase CAMK2 activity | ||
| Aldosterone agonist-progestins | Predicted to increase CAMK2 activity by ↑ROS (Erickson 2014) | Contraceptive |
| Haloperidol | Predicted to increase CAMK2 activity by ↑CAMK2 activity by unclear mechanism (Meshul and Tan 1994; Rushlow et al., 2009) | Psychosis |
| Calcium/vitamin D | Predicted to increase CAMK2 activity by ↑Ca++ | Mineral/ dietary supplement |
| Digoxin | Predicted to increase CAMK2 activity by ↑Na+/Ca++ exchange, increasing Ca++ (heart) (Gonano et al., 2011) | Heart failure |
| ↑RyR CICR (heart) (Gonano et al., 2011) | ||
| SSRIs | Predicted to increase CAMK2 activity by ↑presynaptic CAMK2A phosphorylation by unknown mechanism (Celano et al., 2003; Tiraboschi et al., 2004) | Depression |
| Tricyclics | Predicted to increase CAMK2 activity by ↑presynaptic CAMK2A phosphorylation by unknown mechanism (Celano et al., 2003; Tiraboschi et al., 2004) | Depression, headache prophylaxis, control of nerve pain |
| Tacrolimus | Predicted to increase CAMK2 activity by ↑CAMK2 by ↓calcineurin | Immune suppression |
Table 1 Each medication’s action on CAMK2 is hypothesized by authors based on known mechanisms. Labels: Alphabetic labels refer to the site of proposed activity depicted in Figure 2.
Abbreviations: ROS, reactive oxygen species; GABA-AR, GABA-A receptor; GABA-BR, GABA-B receptor; Ca++, calcium; NOS, nitric oxide species; RyR, ryanodine receptor; Na+, sodium; CICR, calcium initiated calcium release.