Organophosphates irreversibly and non-competitively inhibit acetylcholinesterase, causing poisoning by phosphorylating the serine hydroxyl residue on AChE, which inactivates AChE. AChE is critical for nerve function, so the inhibition of this enzyme, which causes acetylcholine accumulation, results in muscle overstimulation. This causes disturbances across the cholinergic synapses and can only be reactivated very slowly, if at all. Paraoxonase (PON1) is a key enzyme involved in OP toxicity and has been found to be critical in determining an organisms sensitivity to OP exposure. PON1 can inactivate some OPs through hydrolysis. PON1 hydrolyzes the active metabolites in several OP insecticides such as chlorpyrifos oxon, and diazoxon, as well as, nerve agents such as soman, sarin, and VX. PON1 hydrolyzes the metabolites, not the parent compounds of insectides. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of OP exposure. Higher levels of PON1 plasma hydrolytic activity provide a greater degree of protection against OP pesticides. Rats injected with purified PON1 from rabbit serum were more resistant to acute cholinergic activity than the control rats. PON1 knockouts in mice are found to be more sensitive to the toxicity of pesticides, like chlorpyrifos. Animal experiments indicate that while PON1 plays a significant role in regulating the toxicity of OPs its degree of protection given depends on the compound (i.e. Chlorpyrifos oxon or diazoxon).
The lawsuit claimed that Par marketed the product as effective for this use, despite having conducted no well-controlled studies to support a claim of greater efficacy for Megace ES, and prior knowledge of the severe adverse side effects for geriatric patients, including deep vein thrombosis, toxic reactions with impaired renal function, and mortality. Society and culture
Generic names
Megestrol acetate is the generic name of the drug and its INNM, USAN, USP, and BANM, while megestrol is the INN and BAN and mégestrol the DCF of megestrol, the free alcohol form of MGA. The medication is also known by its developmental code names BDH-1298, NSC-71423, and SC-10363. Brand names
MGA is marketed under a variety of brand names throughout the world but is most commonly sold under the brand name Megace. It is also available under the brand name Megace ES in the United States and under the brand name Megace OS in Canada. For use in veterinary medicine, MGA is sold as Ovaban in the United States and as Ovarid in the United Kingdom. Availability
MGA is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, Australia, New Zealand, Latin America, Asia, and a few African countries. It does not appear to be marketed in Germany, Russia, South Africa, Japan, India, or Mexico, among other countries. Generation
Progestins in birth control pills are sometimes grouped by generation.