simply RED
April 11th, 2008, 04:38 PM
Synergism (in terms of toxicology) is called the simultaneous action of two or more agents in order to produce toxic effect, greater then their additive effect. Synergism is most pronounced among CNS (Nerve) toxins.
For example - almost all toxic agents that have agonistic action on inhibitory mechanisms in CNS multiply their effect when administrated simultaneously.
- GABA agonists (barbiturates), sensitisers (benzodiazepines), analogs
- Opioid agonists (mu opioids) (fentanyl, morphine)
- Meds with different action (sodium channel blockers, enzyme inhibitors, adrenaline, noradrenaline, dopamine or serotonine antagonists) (tegretol, valproic acid, neuroleptics)
Especially dangerous is the combination of opioid agonists and phenothiazine neuroleptics (like http://en.wikipedia.org/wiki/Chlorpromazine).
Also the combination of tegretol (carbamazepine) and valproate.
Also the combination of barbiturates with ethanol or methanol.
The combination of barbiturates and methanol is untreatable. The antidote for methanol being ethanol is synergically toxic with barbiturates
(both acting on GABA-A).
Also the combination of benzodizepines and barbiturates.
On the other hand - toxic agents that have agonistic action on some excitatory CNS mechanisms also multiply their effect when administrated simultaneously.
- Adrenergic agonists (clenbuterol http://en.wikipedia.org/wiki/Clenbuterol )
- Noradrenaline, dopamine or serotonine agonists (tricyclic antidepresants, amphetamines, LSD, MAO inhibitors)
Especially lethal is the combination of clenbuterol, amphetamine and MAO inhibitors. It is very possible that GABA antagonists Cl channel blockers (picrotoxine, bicyclophosphates) could be synergistic with this combination. Especially with clenbuterol. Hearth Digitalis glycosides are also dangerous with amphetamine or clen.
Lethal is the combination of tricyclic antidepresants, amphetamines and MAO inhibitors.
It is also interesting to spot that barbiturate (GABA agonist) coma can be treated with picrotoxine (Cl channel blocker). Like aceylcholinesterase inhibitors intoxications are treated with atropine (antagonist of the muscarinic acetylcholine receptor).
An interesting "exception" is the synergism of barbiturates and thiophosphates, like parathion + phenobarbital. Barbiturates induce P450-izoenzymes, which metabolizes P=S to P=O and transform the thiophosphates into their active metabolites.
All toxins that damage the liver act in synergism with the current available standard chemical weapons and pesticides. So, phosgene, iprite, chloropicrine, lewisite can be diluted with some chlorinated hydrocarbon (tetracholoromethane for example) especially if they have to be used in enclosed space. The mix of the main ingredient and the diluting Cl-hydrocarbon should save funds and make the mix more stable and useful with a bursting high explosive charge. Aceylcholinesterase inhibitors like VX, sarin, soman should act in synergism with GABA antagonists (t-butyl-bicyclophosphate, caged convulsants) since the combination should worsen the seizures.
Dioxines (TCDD for example) act in synergism with all CW agents. So, a portion of dioxine (10-20%) added to the mix should contribute to the effects. Since dioxine is easy to produce from sodium (1,3,5) or (1,3,4) trichlorophenolate with heating to 250-300 degrees in hydrocarbon (or chlorinated) solvent. Dioxine and iprite or diphosgene should be a great combination.
Another advantage of using synergism in CWs is that it makes them more treatment resistant.
For example - almost all toxic agents that have agonistic action on inhibitory mechanisms in CNS multiply their effect when administrated simultaneously.
- GABA agonists (barbiturates), sensitisers (benzodiazepines), analogs
- Opioid agonists (mu opioids) (fentanyl, morphine)
- Meds with different action (sodium channel blockers, enzyme inhibitors, adrenaline, noradrenaline, dopamine or serotonine antagonists) (tegretol, valproic acid, neuroleptics)
Especially dangerous is the combination of opioid agonists and phenothiazine neuroleptics (like http://en.wikipedia.org/wiki/Chlorpromazine).
Also the combination of tegretol (carbamazepine) and valproate.
Also the combination of barbiturates with ethanol or methanol.
The combination of barbiturates and methanol is untreatable. The antidote for methanol being ethanol is synergically toxic with barbiturates
(both acting on GABA-A).
Also the combination of benzodizepines and barbiturates.
On the other hand - toxic agents that have agonistic action on some excitatory CNS mechanisms also multiply their effect when administrated simultaneously.
- Adrenergic agonists (clenbuterol http://en.wikipedia.org/wiki/Clenbuterol )
- Noradrenaline, dopamine or serotonine agonists (tricyclic antidepresants, amphetamines, LSD, MAO inhibitors)
Especially lethal is the combination of clenbuterol, amphetamine and MAO inhibitors. It is very possible that GABA antagonists Cl channel blockers (picrotoxine, bicyclophosphates) could be synergistic with this combination. Especially with clenbuterol. Hearth Digitalis glycosides are also dangerous with amphetamine or clen.
Lethal is the combination of tricyclic antidepresants, amphetamines and MAO inhibitors.
It is also interesting to spot that barbiturate (GABA agonist) coma can be treated with picrotoxine (Cl channel blocker). Like aceylcholinesterase inhibitors intoxications are treated with atropine (antagonist of the muscarinic acetylcholine receptor).
An interesting "exception" is the synergism of barbiturates and thiophosphates, like parathion + phenobarbital. Barbiturates induce P450-izoenzymes, which metabolizes P=S to P=O and transform the thiophosphates into their active metabolites.
All toxins that damage the liver act in synergism with the current available standard chemical weapons and pesticides. So, phosgene, iprite, chloropicrine, lewisite can be diluted with some chlorinated hydrocarbon (tetracholoromethane for example) especially if they have to be used in enclosed space. The mix of the main ingredient and the diluting Cl-hydrocarbon should save funds and make the mix more stable and useful with a bursting high explosive charge. Aceylcholinesterase inhibitors like VX, sarin, soman should act in synergism with GABA antagonists (t-butyl-bicyclophosphate, caged convulsants) since the combination should worsen the seizures.
Dioxines (TCDD for example) act in synergism with all CW agents. So, a portion of dioxine (10-20%) added to the mix should contribute to the effects. Since dioxine is easy to produce from sodium (1,3,5) or (1,3,4) trichlorophenolate with heating to 250-300 degrees in hydrocarbon (or chlorinated) solvent. Dioxine and iprite or diphosgene should be a great combination.
Another advantage of using synergism in CWs is that it makes them more treatment resistant.