In rats, it triggered the release of vasopressin into paraventricular nucleus of the hypothalamus and decreased the release of ACTH under stress. Pharmacokinetics
Oral administration of 15 to 45 mg of temazepam in humans resulted in rapid absorption with significant blood levels achieved in fewer than 30 minutes and peak levels at two to three hours.In a single- and multiple-dose absorption, distribution, metabolism, and excretion (ADME) study, using tritium-labelled drug, temazepam was well absorbed and found to have minimal (8%) first-pass drug metabolism. No active metabolites were formed and the only significant metabolite present in blood was the O-conjugate. The unchanged drug was 96% bound to plasma proteins. The blood-level decline of the parent drug was biphasic, with the short half-life ranging from 0.4 to 0.6 hours and the terminal half-life from 3.5 to 18.4 hours (mean 8.8 hours), depending on the study population and method of determination.Temazepam has very good bioavailability, with almost 100% being absorbed following being taken by mouth. The drug is metabolized through conjugation and demethylation prior to excretion. Most of the drug is excreted in the urine, with about 20% appearing in the faeces. The major metabolite was the O-conjugate of temazepam (90%); the O-conjugate of N-desmethyl temazepam was a minor metabolite (7%). Chemistry
Temazepam is a benzodiazepine. It is a white, crystalline substance, very slightly soluble in water, and sparingly soluble in alcohol. Synthesis
Pharmacologically active metabolite of diazepam, q.v. N-oxides are prone to undergo the Polonovski rearrangement when treated with acetic anhydride, and this was illustrated by the synthesis of oxazepam.
Kimuras disease is a benign rare chronic inflammatory disorder. Its primary symptoms are subdermal lesions in the head or neck or painless unilateral inflammation of cervical lymph nodes. Cause
Its cause remains unknown. Reasons such as an allergic reaction, tetanus toxoid vaccination, or an alteration of immune regulation are suspected. Other theories like persistent antigenic stimulation following arthropod bites and parasitic or candidal infection have also been proposed. To date, none of these theories has been substantiated. Pathophysiology
The pathophysiology of Kimuras disease remains unknown, although an allergic reaction, trauma, and an autoimmune process have all been implicated as possible causes. The disease is manifested by an abnormal proliferation of lymphoid follicles and vascular endothelium. Peripheral eosinophilia and the presence of eosinophils in the inflammatory infiltrate suggest it may be a hypersensitivity reaction. Some evidence has indicated TH2 lymphocytes may also play a role, but further investigation is needed.Kimuras disease is generally limited to the skin, lymph nodes, and salivary glands, but patients with Kimuras disease and nephrotic syndrome have been reported. The basis of this possible association is unclear. Diagnosis
An open biopsy is the chief means by which this disease is diagnosed. "Lymphoid nodules with discrete germinal centers can occupy an area extending from the reticular dermis to the fascia and muscle. Follicular hyperplasia, marked eosinophilic infiltrate and eosinophilic abscesses, and the proliferation of postcapillary venules are characteristic histological findings. [18] Centrally, thick-walled vessels are present with hobnail endothelial cells. Immunohistochemical evaluation of the lymphoid nodules demonstrates a polymorphous infiltrate without clonality.