Nitration of 2,3-dimethylpyridine N-oxide affords the nitro derivative (the addition of NO2) (2) The newly introduced nitro group is then displaced by the alkoxide from 3-methoxypropanol to yield the corresponding ether (3). Treatment with acetic anhydride results in the Polonovski reaction. Saponification followed by treatment with thionyl chloride then chlorinates the primary alcohol (5). Reaction with benzimidazole-2-thiol (6) followed by oxidation of the resulting thioether to the sulfoxide yields the final product: rabeprazole (8). Physiochemical properties
Rabeprazole is characterized as a white to yellowish-white solid in its pure form. It is soluble in a number of solvents. Rabeprazole is very soluble in water and methanol, freely soluble in ethanol, chloroform, and ethyl acetate, and is insoluble in ether and n-hexane. It is unstable under humid conditions. History
Rabeprazole was first marketed in Europe in 1998. In 1999, one year later, rabeprazole was approved for use in the United States. Development
Developed by Eisai Medical Research by the research names E3810 and LY307640, the pre-investigational new drug application was submitted on October 28, 1998. The final investigational new drug application was submitted August 6, 1999. On August 19, 1999, rabeprazole was approved in the US for multiple gastrointestinal indications. The approval for the treatment of symptomatic gastroesophageal reflux disease was on February 12, 2002. Society and culture
Legal status
Rabeprazole is approved in the United States and the United Kingdom for prescription use only. Rabeprazole was approved in India in December 2001. It was approved in Japan in 1997, and in all European Union member countries since.
They eventually increase in speed and intensity as the orgasm approaches, until a final "plateau" (the orgasmic) pleasure sustained for several seconds.During orgasm, a human male experiences rapid, rhythmic contractions of the anal sphincter, the prostate, and the bulbospongiosus muscles of the penis. The sperm are transmitted up the vas deferens from the testicles, into the prostate gland as well as through the seminal vesicles to produce what is known as semen. The prostate produces a secretion that forms one of the components of ejaculate. Except for in cases of a dry orgasm, contraction of the sphincter and prostate force stored semen to be expelled through the peniss urethral opening. The process takes from three to ten seconds, and produces a pleasurable feeling. Ejaculation may continue for a few seconds after the euphoric sensation gradually tapers off. It is believed that the exact feeling of "orgasm" varies from one man to another. After ejaculation, a refractory period usually occurs, during which a man cannot achieve another orgasm. This can last anywhere from less than a minute to several hours or days, depending on age and other individual factors. Females
A womans orgasm may, in some cases, last a little longer than a mans. Womens orgasms have been estimated to last, on average, approximately 20 seconds, and to consist of a series of muscular contractions in the pelvic area that includes the vagina, the uterus, and the anus.