Vasoconstrictor

Naturally Occurring Compounds. Many derivatives of iadole are found ia plants and animals where they are derived from the amino acid tryptophan. Several of these have important biological function or activity. Serotonin [50-67-9] (12) functions as a neurotransmitter and vasoconstrictor (35). Melatonin [73-31-4] (13) production is controlled daily by the circadian cycle and its physiological level iafluences, and seasonal rhythms ia humans and other species (36). Indole-3-acetic acid [87-51-4] (14) is a plant growth stimulant used ia several horticultural appHcations (37). 

Lidocaine hydrochloride [73-78-9] (Xylocaine), is the most versatile local anesthetic agent because of its moderate potency and duration of action, rapid onset, topical activity, and low toxicity. Its main indications are for infiltration, peripheral nerve blocks, extradural anesthesia, and in spinal anesthesia where a duration of 30 to 60 min is desirable. Because of its vasodilator activity, addition of the vasoconstrictor, epinephrine, increases the duration of action of Hdocaine markedly. It is also available in ointment or aerosol preparations for a variety of topical appHcations. 

Kidney Function. Prostanoids influence a variety of kidney functions including renal blood flow, secretion of renin, glomerular filtration rate, and salt and water excretion. They do not have a critical role in modulating normal kidney function but play an important role when the kidney is under stress. Eor example, PGE2 and -I2 are renal vasodilators (70,71) and both are released as a result of various vasoconstrictor stimuli. They thus counterbalance the vasoconstrictor effects of the stimulus and prevent renal ischemia. The renal side effects of NSAIDS are primarily observed when normal kidney function is compromised. 

Sorbitan sesquioleate emulsions of petrolatum and wax are used as ointment vehicles in skin treatment. In topical appHcations, the inclusion of both sorbitan fatty esters and their poly(oxyethylene) derivatives modifies the rate of release and promotes the absorption of antibiotics, antiseptics, local anesthetics, vasoconstrictors, and other medications from suppositories, ointments, and lotions. Poly(oxyethylene(20)) sorbitan monooleate, also known as Polysorbate 80 (USP 23), has been used to promote absorption of ingested fats from the intestine (245). 

Phenylephrine. Phenylephrine hydrochloride is an a -adrenoceptor agonist. Phenylephrine produces powerful vasoconstrictor and hypertensive responses. This results in baroreceptor activation of a reflex bradycardia and thus is useful in the treatment of supraventricular tachyarrhythmias. Unlike epinephrine [51-43-4] the actions of which are relatively transient, phenylephrine responses are more sustained (20 min after iv dosing and 50 min after subcutaneous dosing) (86). 

Prazosin, a selective a -adrenoceptor antagonist, exerts its antihypertensive effect by blocking the vasoconstrictor action of adrenergic neurotransmitter, norepinephrine, at a -adrenoceptors in the vasculature (200,227,228). Prazosin lowers blood pressure without producing a marked reflex tachycardia. It causes arteriolar and venular vasodilation, but a significant side effect is fluid retention. Prazosin increases HDL cholesterol, decreases LDL cholesterol, and does not cause glucose intolerance. 

The homolog of epinephrine in this series is a potent vasoconstrictor. Reaction of 3,4-dimethoxypropiophenone with butyl nitrite leads to nitrosation at the a position (36). Stepwise reduction of the nitrosoketone leads to the amino alcohol (37). Removal of the methyl ether affords racemic 38. Resolution of this last followed by separation of the (-) isomer gives levonor-defrine (38). ... 

Vasoconstrictor. A drug that causes a contraction of the vascular smooth muscle, thus increasing the resistance to blood flow. 

Therapeutic Function Vasoconstrictor Chemical Name 8-L-Ornithinevesopressln Common Name —... 

FIGURE 9.14 Effects of adenosine receptor agonist 2-chloro-adenosine on vascular perfusion pressure of isolated perfused rat kidneys. Minor effects seen in untreated kidneys (filled circles) and pronounced vasoconstriction while vasodilatation in kidneys coperfused with subthreshold concentrations of a-adrenoceptor vasoconstrictor methoxamine and vasodilatatory activation of adenylyl cyclase with forskolin (open circles). Redrawn from [49]. 

As endothelins mediate potent vasoconstrictor effects, ECE inhibitors and endothelin receptor antagonists were developed for the treatment of cardiovascular diseases, such as acute and chronic heart failure, pulmonary hypertension and subarachnoid haemorrhage. As ETa recqrtors have potent mitogenic responses and may promote progression of ovarian and prostate cancer and bone metastases ETA receptors are also considered as a potential targets for anti-tumour activity. 

Yanagisawa M, Rurihara H, Kimura S et al (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332 411-415... 

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

Vasoconstrictors are drugs which increase the tone of smooth muscle cells in the vasculature. They include sympathomimetic amines and certain eicosanoids and peptides (angiotensin, vasopressin, urotensin or en-dothelin). 

---