pyrethroids

Pyrethroids, synthetic versions of natural compounds found in flowers, are used extensively in pesticides. At low doses, they alter hormones.

Pyrethroids have been considered safer than DDT and chlordane because they did not seem to build up in the environment.

Pyrethroids are the second most common class of pesticide that results in poisoning. In high doses, pyrethroids are toxic to the nervous system.

The pyrethroid compounds are used in large volumes in farm and household pesticides and are sprayed by public agencies to kill mosquitoes.

phenothiazine

antiPsychotics = neuroleptics

Long term use of neuroleptics is linked to visible shrinkage of the frontal lobes - the part of the brain used for higher level thought.

1876 An aniline dye methylene blue, a derivative of phenothiazine, is synthesized by Heinrich Caro at BASF.

1883 Heinrich August Bernthsen synthesized phenothiazine S(C₆H₄)₂NH.

mid 1880s Paul Ehrlich began to use methylene blue in his cell staining experiments that led to pioneering discoveries about different cell types.

1890s Methylene blue is being used to treat malaria.

1935 DuPont introduced the chemical phenothiazine as an insecticide.

The term "phenothiazines" describes the largest of the five main classes of neuroleptic antiPsychotic chemicals.

It is claimed these chemicals have antiPsychotic and antiemetic properties.

Phenothiazine may cause severe side effects such as akathisia (inability to remain motionless), tardive dyskinesia (involuntary repetitive movements) as well as other extrapyramidal symptoms such as an inability to move, and the rare but potentially fatal neuroleptic malignant syndrome as well as substantial weight gain.

Tardive dyskinesia appears to be related to damage to the part of the nervous system that uses and processes the neurotransmitter dopamine.

Targeting the receptor CB₂ in a mouse model of l-dopa induced dyskinesia

Phenothiazine antiPsychotics are classified into three groups that differ with respect to the substituent on nitrogen:

the aliphatic compounds (bearing acyclic groups);

the "piperidines" (bearing piperidine-derived groups);

and the piperazine (bearing piperazine-derived substituents).

Aliphatic compounds

Chlorpromazine marketed as Thorazine®, Chlor-PZ®, Klorazine®, Promachlor®, Promapar®, Sonazine®, Chlorprom®, Chlor-Promanyl®, Largactil®.

Promazine marketed as Sparine®

Triflupromazine marketed as Stelazine®, Clinazine®, Novaflurazine®, Pentazine®, Terfluzine®, Triflurin®, Vesprin®

Levomepromazine/Methotrimeprazine marketed as Nozinan®, Levoprome®

Piperidines

Mesoridazine marketed as Serentil®

Thioridazine marketed as Mellaril®, Novoridazine®, Thioril®

Piperazines

Fluphenazine marketed as Prolixin®, Permitil®, Modecate®, Moditen®

Perphenazine marketed as Trilafon®, Etrafon®, Triavil®, Phenazine®

Flupentixol marketed as Depixol®, Fluanxol®

Prochlorperazine marketed as Compazine®, Stemetil®®

Trifluoperazine marketed as Stelazine®

Most phenothiazines act as strong central nervous system sedatives.

Examples of phenothiazine antiPsychotics are: prochlorperazine (Compazine®, Compro®, Procomp®), chlorpromazine (Promapar®, Thorazine®), fluphenazine (Permitil®, Prolixin®), perphenazine, trifluoperazine (Stelazine®), thioridazine (Mellaril®) and mesoridazine (no longer available in the United States).

Long term use of neuroleptics shows visible shrinkage of the frontal lobes - the part of the brain used for rational thought, the same part targeted by the frontal lobotomy and electroshock treatments.

1944 3,500,000 pounds of phenothiazine is sold in the US.

Phenothiazine use declines after 1944 as it quickly degrades in sunlight and air, so it is difficult to determine how much to use in the field.

Phenothiazine is largely replaced by DDT which is more durable.

1959 Mornidine®, also known as Pipamazine, is introduced into the US market by GD Searle & Company.

Pipamazine (trade names: Mornidine®, Mometine®, Nausidol®), of the phenothiazine class, is chemically related to chlorpromazine, but has negligible antipsychotic activity and produces few extrapyramidal side effects.

Trials found that hypotension (low blood pressure) was a substantial concern when the drug was given at normal dosages.

Withdrawn from the US market in 1969, after reports of hepatotoxicity.

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