Nefazodone has low but significant affinity for the serotonin, norepinephrine, and dopamine transporters as well, and therefore acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has low but potentially significant affinity for the histamine H1 receptor, where it is an antagonist, and hence may have some antihistamine activity. Nefazodone has negligible activity at muscarinic acetylcholine receptors, and accordingly, has no anticholinergic effects. Pharmacokinetics
The bioavailability of nefazodone is low and variable, about 20%. Its plasma protein binding is approximately 99%, but it is bound loosely.Nefazodone is metabolized in the liver, with the main enzyme involved thought to be CYP3A4. The drug has at least four active metabolites, which include hydroxynefazodone, para-hydroxynefazodone, triazoledione, and meta-chlorophenylpiperazine. Nefazodone has a short elimination half-life of about 2 to 4 hours. Its metabolite hydroxynefazodone similarly has an elimination half-life of about 1.5 to 4 hours, whereas the elimination half-lives of triazoledione and mCPP are longer at around 18 hours and 4 to 8 hours, respectively. Due to its long elimination half-life, triazole is the major metabolite and predominates in the circulation during nefazodone treatment, with plasma levels that are 4 to 10 times higher than those of nefazodone itself. Conversely, hydroxynefazodone levels are about 40% of those of nefazodone at steady state. Plasma levels of mCPP are very low at about 7% of those of nefazodone; hence, mCPP is only a minor metabolite.
The study showed that 45.5 people out of 100,000 had been diagnosed with hypopituitarism, with 4.2 new cases per year. 61% were due to tumors of the pituitary gland, 9% due to other types of lesions, and 19% due to other causes; in 11% no cause could be identified.Recent studies have shown that people with a previous traumatic brain injury, spontaneous subarachnoid hemorrhage (a type of stroke) or radiation therapy involving the head have a higher risk of hypopituitarism. After traumatic brain injury, as much as a quarter have persistent pituitary hormone deficiencies. Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition. It is therefore possible that many cases of hypopituitarism remain undiagnosed, and that the annual incidence would rise to 31 per 100,000 annually if people from these risk groups were to be tested. History
The pituitary was known to the ancients, such as Galen, and various theories were proposed about its role in the body, but major clues as to the actual function of the gland were not advanced until the late 19th century, when acromegaly due to pituitary tumors was described. The first known report of hypopituitarism was made by the German physician and pathologist Dr Morris Simmonds. He described the condition on autopsy in a 46-year-old woman who had had severe puerperal fever eleven years earlier, and subsequently had amenorrhea, weakness, signs of rapid aging, and anemia.