Prior to 1922, Doctors McCray and McClintic both died while doing research on Rocky Mountain spotted fever, as did an aide of Noguchi Hideyo at the Rockefeller Institute. Research began in 1922 in western Montana, in the Bitterroot Valley around Hamilton, Montana, after the Governors daughter and his son-in-law died of the fever. However, prior to that, in 1917, Dr. Lumford Fricks introduced herds of sheep into the Bitterroot Valley. His hypothesis was that the sheep would eat the tall grasses where ticks lived and bred. Past Assistant Surgeon R.R. Spencer of the Hygienic Laboratory of the U.S. Public Health Service was ordered to the region, and he led a research team at an abandoned schoolhouse through about 1924. Spencer was assisted by R. R. Parker, Bill Gettinger, Henry Cowan, Henry Greenup, Elmer Greenup, Gene Hughes, Salsbury, Kerlee, and others, of whom Gettinger, Cowan and Kerlee died of Rocky Mountain spotted fever. Through a series of discoveries, the team found that a previous blood meal was necessary to make the tick deadly to its hosts, as well as other facets of the disease. On May 19, 1924, Spencer put a large dose of mashed wood ticks, from lot 2351B, and some weak carbolic acid into his arm by injection.
Side effects
The adverse effects include drowsiness, dizziness, confusion, constipation, anxiety, nausea, blurred vision, restlessness, decreased coordination, dry mouth, shallow breathing, hallucinations, irritability, problems with memory or concentration, tinnitus and trouble urinating. Chlorphenamine produces less sedation than other first-generation antihistamines.A large study on people 65 years old or older, linked the development of Alzheimers disease and other forms of dementia to the "higher cumulative" use of chlorphenamine and other first-generation antihistamines, due to their anticholinergic properties. Pharmacology
Pharmacodynamics
Chlorphenamine acts primarily as a potent H1 antihistamine. It is specifically a potent inverse agonist of the histamine H1 receptor. The drug is also commonly described as possessing weak anticholinergic activity by acting as an antagonist of the muscarinic acetylcholine receptors. The dextrorotatory stereoisomer, dexchlorpheniramine, has been reported to possess Kd values of 15 nM for the H1 receptor and 1,300 nM for the muscarinic acetylcholine receptors in human brain tissue. The smaller the Kd value, the greater the binding affinity of the ligand for its target. In addition to acting as an inverse agonist at the H1 receptor, chlorphenamine has been found to act as a serotonin reuptake inhibitor (Kd = 15.2 nM for the serotonin transporter). It has only weak affinity for the norepinephrine and dopamine transporters (Kd = 1,440 nM and 1,060 nM, respectively).