Other neurotransmitters, peptides, hormones, and enzymes
Acute amphetamine administration in humans increases endogenous opioid release in several brain structures in the reward system. Extracellular levels of glutamate, the primary excitatory neurotransmitter in the brain, have been shown to increase in the striatum following exposure to amphetamine. This increase in extracellular glutamate presumably occurs via the amphetamine-induced internalization of EAAT3, a glutamate reuptake transporter, in dopamine neurons. Amphetamine also induces the selective release of histamine from mast cells and efflux from histaminergic neurons through VMAT2. Acute amphetamine administration can also increase adrenocorticotropic hormone and corticosteroid levels in blood plasma by stimulating the hypothalamic–pituitary–adrenal axis.In December 2017, the first study assessing the interaction between amphetamine and human carbonic anhydrase enzymes was published; of the eleven carbonic anhydrase enzymes it examined, it found that amphetamine potently activates seven, four of which are highly expressed in the human brain, with low nanomolar through low micromolar activating effects. Based upon preclinical research, cerebral carbonic anhydrase activation has cognition-enhancing effects; but, based upon the clinical use of carbonic anhydrase inhibitors, carbonic anhydrase activation in other tissues may be associated with adverse effects, such as ocular activation exacerbating glaucoma. Pharmacokinetics
The oral bioavailability of amphetamine varies with gastrointestinal pH; it is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine. Amphetamine is a weak base with a pKa of 9.9; consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium.
Differential diagnosis
The differential diagnosis histologically includes rhabdomyosarcoma, granular cell tumor, alveolar soft part sarcoma, hibernoma, oncocytoma, and crystal storing histiocytosis, among others. Management
Surgical excision is the treatment of choice. Recurrences are reported, but this is usually due to incomplete removal initially. There is no role for chemotherapy or radiation therapy. Epidemiology
They present over a wide age range (birth to about 65 years), but within the head and neck region, about 50% of cases develop in patients younger than 15 years of age. Within the head and neck, males are affected about 2–3 times more often than females. == References ==