Carbachol, also known as carbamylcholine and sold under the brand name Miostat among others, is a cholinomimetic drug that binds and activates acetylcholine receptors. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery. It is generally administered as an ophthalmic solution (i.e., eye drops). Carbachol produces effects comparable to those of sarin if a massive overdose is administered (as may occur following industrial and shipping accidents) and therefore it is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.It is on the World Health Organizations List of Essential Medicines. Chemistry and pharmacology
Carbachol is a choline carbamate and a positively charged quaternary ammonium compound. It is not well absorbed in the gastro-intestinal tract and does not cross the blood–brain barrier. It is usually administered topical ocular or through intraocular injection. Carbachol is not easily metabolized by cholinesterase, it has a 2 to 5 minute onset of action and its duration of action is 4 to 8 hours with topical administration and 24 hours for intraocular administration. Since carbachol is poorly absorbed through topical administration, benzalkonium chloride is mixed in to promote absorption.Carbachol is a parasympathomimetic that stimulates both muscarinic and nicotinic receptors.
History
Viltolarsen was developed by Nippon Shinyaku and the NCNP based on pre-clinical study conducted by Toshifumi Yokota and colleagues, and evaluated in two clinical studies with a total of 32 participants, all of whom were male and had genetically confirmed DMD. The increase in dystrophin production was established in one of those two studies, a study that included sixteen DMD participants, with eight participants receiving viltolarsen at the recommended dose. In the study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25. Trial 1 provided data for evaluation of the benefits of viltolarsen. The combined populations from both trials provided data for evaluation of the side effects of viltolarsen. Trial 1 was conducted at six sites in the United States and Canada and Trial 2 was conducted at five sites in Japan. All participants in both trials were on a stable dose of corticosteroids for at least three months before entering the trials.The U.S. Food and Drug Administration (FDA) concluded that the applicants data demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in people with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. A clinical benefit of the drug has not been established.