Chemical antagonism

A particularly volatile Issue is that of hormone-mimicking or antagonizing chemicals. Books, articles In the news, and television programs including one on the Public Broadcasting Service (PBS) have raised the public awareness of endocrine disrupters. Endocrine disrupters are those chemicals that affect hormonal secretions by the endocrine system of the human body. There is considerable scientific uncertainty about the effects of these substances, but public concern sometimes drives policy even without a scientific basis. 

Antagonism is appHed to a situation where two chemicals, given together, interfere with each other s action or where one interferes with the action of the other. The result will usually be a decrease in toxic injury. A special case of antagonism is in studies on antidotal action. 

Amensalism (antagonism) Production of a substance by one organism that is inhibitory to one or more other organisms. The terms antibiosis and allelopathy also describe cases of chemical inhibition. 

Drugs that should not be combined due to overlapping toxi-cities include amprenavir oral solution plus ritonavir oral solution, atazanavir plus indinavir (due to enhanced hyperbilirubinemia), and any combination of didanosine, stavudine, and zalcitabine. Emtricitabine and lamivudine should not be combined because of their similar chemical structures, and antagonism can result when lamivudine is combined with zalcitabine, or stavudine is combined with zidovudine. 

Chemical antagonism results when two drugs combine with each other chemically and the activity of one or both is blocked. For example, dimer-caprol chelates lead and reduces the toxicity of this heavy metal. Compeli-... 

Finally, the chemistry of the organism must be taken into account. Interrelationships among metals can rarely be explained on a purely chemical basis (i.e. inhibition of the uptake of the metal of interest and uptake of the competing metal). Even metals exhibiting the expected chemical antagonisms, may also initiate a cellular feedback, alter the overall biological metabolism or modify membrane permeability or the cells capacity to deal with the metal of interest. 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

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