Fig. 2

Summary of the test chemicals and experimental exposure conditions used in the current study. Information shown left to right: compound name; strength of the association with seizure induction in mammals (see below); Chemical Abstracts Service (CAS) registry number; abbreviation as used in other figures; pharmacological class; primary mechanism of action; and exposure concentration and times used the Ca2+ imaging. The strength of the association with seizure induction in mammals based on the scientific literature is classified as follows: A - strong link—tool compounds/precipitants; B - clear association in clinic/nonclinical studies; C - measurable association in clinic and/or some nonclinical evidence; D - limited clinical/non clinical data, but weak or conflicting and/or seizure-inducing only under specific circumstances (e.g., overdose or withdrawal); E - mechanistic link only, no published confirmatory data; and F - no known link to seizures (seizure negative). Abbreviations: AChE = acetylcholine esterase; DR = dopamine receptor; αR = α-adrenoreceptor; HR = histamine receptor; mAChR = muscarinic acetylcholine receptor; 5-HTR = 5-hyroxytryptamine receptor; GABAR = γ-aminobutyric acid receptor; KAR = kainic acid receptor; NMDAR = glutamatergic N-methyl-d-aspartate receptor; GLYR = glycine receptor; Kv = voltage-gated K+ channel; NA = noradrenaline; DA = dopamine; 5-HT = 5-hyroxytryptamine (serotonin); P1 = adenosine receptor; PDE = phosphodiesterase; μ/δ-opioidR = mu/delta-opioid receptor; LOQ = limit of quantification. *DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate); **cis-ACPD ((±)-1-Aminocyclopentane-cis-1,3-dicarboxylic acid); ***XE991 (10,10-bis(4-Pyridinylmethyl) -9(10H)-anthracenone dihydrochloride); ****PF-06767832 (1,5-Anhydro-2,3-dideoxy-3-[[[5-methyl-4-[[4-(4-thiazolyl)phenyl]methyl]-2-pyridinyl]carbonyl]amino]-l-threo-pentitol, N-((3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl)-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]-pyridine-2-carboxamide); *****SNC80 ((+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide); ******SB205607 or TAN-67, ((R*,S*)-(±)-2-methyl-4aa-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aa-octahydroquinolino[2,3,3-g]isoquinoline dihydrobromide); *******BW373U86 4-[(αR*)-α-((2S*,5R*)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl]-N,N-diethylbenzamide). All test chemicals were obtained from sigma-Aldrich (Gillingham, UK) or Tocris (Bristol, UK)