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Environmental Sciences Europe

Table 2 Compounds with neuroactive mode of action that were found during large-scale chemical analysis of samples from three European river basins (Danube, Rhine, Mulde/Saale)

From: An ecotoxicological view on neurotoxicity assessment

MIE

Compound name

HQ histogram fish

HQ histogram daphnia

Captured in AOP-wiki?

Reported species specificity

All

n/a

n/a

n/a

Acetylcholinesterase inhibition

Triphenylphosphate, rivastigmine, tris(1,3-dichloroisopropyl)phosphate (TDCPP), carbofuran, carbetamide, methomyl, methiocarb, pirimicarb, ethyl-azinphos, chlorpyrifos, diazinon, chlorfenvinphos, chlorpyrifos-methyl, dimethoate, carbaryl, TMPP (tris (methyl phenyl) phosphate)

Yes

Conserved among vertebrates and invertebrates [298]

GABA receptor antagonism

Fipronil

Similar (non-competitive GABA receptor blocking)

Compound-specific differences in target sensitivity [306]

Serotonin reuptake inhibition, leading to stimulation of serotonergic neurons

N,O-didesmethyl venlafaxine, citalopram, O-desmethylvenlafaxine, venlafaxine

Yes

Human pharmaceuticals but potential neuroendocrine effects in invertebrates [307]

Antagonism of serotonin, dopamine and/or alpha-adrenoreceptors

Metoclopramide, trimipramine

Not available

 

Opioid receptor agonism

Tramadol, morphine, codeine, methadone

Yes

 

Nicotinic acetylcholine receptor (nAChR) agonism

Thiacloprid, acetamiprid, imidacloprid, levamisol, thiamethoxam, clothianidin, cotinine

Yes

Specific for Insects,in contrast to parent compound nicotine [308])

Enhancement of GABA action via allosteric binding to GABA receptor

Primidone, flunitrazepam, diazepam, midazolam, oxazepam, pentobarbital, lorazepam

Not available

 

NMDA-type glutamate receptor antagonism

Dextromethorphan, ketamine, 1-adamantylamine

(only for agonism)

 

Inhibition of adenosine receptor (CNS stimulation)

Clopidogrel (and derivatives), caffeine

Not available

 

Dopamine reuptake inhibition, leading to stimulation of dopaminergic neurons

Bupropion, cocaine

Not available

 

Dopamine receptor antagonism

Sulpiride, amisulpride

Not available

 

Voltage gated sodium channel antagonism

Lidocaine, carbamazepine (including derivatives), lamotrigine

 

Yes

 

Release of serotonin, dopamine and noradrenaline

MDMA/methylendioxymethamphetamine, MDEA/3,4-methylenedioxyethamphetamine

Not available

 

Proliferation and differentiation of dopaminergic nerve cells

Simazinea

Not available

 

Inhibition of monoamine oxidase (leading to reduced metabolism and hence, increased levels of serotonin and noradrenaline)

Moclobemide

Not available

 

Voltage gated calcium channel inhibition (reduces release of transmitters such as glutamate or noradrenaline)

Pregabalin, gabapentin, gabapentin-lactam

Not available

 
  1. Compounds were grouped according to a common target and molecular initiating event (MIE). Data were extracted from Busch et al. and supplemented with more details on the major reported mechanism of action. Note that the mechanism of action can be highly species-specific but that species specificity is often not known. Hazard quotients (HQ = measured environmental concentration/effect concentration) represent predicted values (baseline toxicity multiplied by a factor of 10 or 100 for non-narcotic compounds) if no measured effect concentrations were available (please refer to Busch et al. for further details). Higher log HQs (close to zero) indicate that environmental concentrations are likely to cause a biological effect. Note that all AOPs of the AOP-Wiki (http://www.aopwiki.org) are under development
  2. aSimazine is a herbicide, but strong evidence for a neurotoxic mode of action in non-target organisms was reported [304]
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