Imidazoline use in sinonasal surgery.

The nasal mucosa is very vascular, receiving more blood flow per cubic centimeter of tissue than does muscle, brain or liver (Drettner and Aust, 1974; [1]). This vascularity can present a major problem during sinus surgery. Surgeons routinely use topical vasoconstrictors in endoscopic sinus surgery however, the optimal regimen is not clear. Imidazoline nasal sprays are often used up to 1hour before sinonasal surgery to aid in intraoperative vasoconstriction. After the induction of anaesthesia, epinephrine-based topical and submucosal preparations are subsequently administered to further enhance vasoconstriction. Imidazolines are non-selective, partial alpha adrenoceptor agonists with a higher affinity, yet lower potency, for alpha adrenoceptors when compared to epinephrine. It is hypothesized that imidazolines block the action of epinephrine on the alpha adrenoceptors of the nasal mucosa resulting in less vasoconstriction, and a poorer intra-operative field, when compared to the use of epinephrine alone. This paper hypothesizes that preoperative imidazoline administration may adversely affect optimal intra-operative vasoconstriction.

Imidazoline antihypertensive drugs: selective i(1) -imidazoline receptors activation.

Involvement of imidazoline receptors (IR) in the regulation of vasomotor tone as well as in the mechanism of action of some centrally acting antihypertensives has received tremendous attention. To date, pharmacological studies have allowed the characterization of three main imidazoline receptor classes, the I(1) -imidazoline receptor which is involved in central inhibition of sympathetic tone to lower blood pressure, the I(2) -imidazoline receptor which is an allosteric binding site of monoamine oxidase B (MAO-B), and the I(3) -imidazoline receptor which regulates insulin secretion from pancreatic ß-cells. All three imidazoline receptors represent important targets for cardiovascular research. The hypotensive effect of clonidine-like centrally acting antihypertensives was attributed both to α(2) -adrenergic receptors and nonadrenergic I(1) -imidazoline receptors, whereas their sedative action involves activation of only α(2) -adrenergic receptors located in the locus coeruleus. Since more selective I(1) -imidazoline receptors ligands reduced incidence of typical side effects of other centrally acting antihypertensives, there is significant interest in developing new agents with higher selectivity and affinity for I(1) -imidazoline receptors. The selective imidazoline receptors agents are also more effective in regulation of body fat, neuroprotection, inflammation, cell proliferation, epilepsy, depression, stress, cell adhesion, and pain. New agonists and antagonists with high selectivity for imidazoline receptor subtypes have been recently developed. In the present review we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the theoretical studies of imidazoline receptor ligands.

A new class of analgesic agents toward prostacyclin receptor inhibition: synthesis, biological studies and QSAR analysis of 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines.

By studying the structural similarity of analgesic imidazolines and 2-phenylnitronyl nitroxides, 20 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazolines (2a-t) were newly synthesized as selective antagonists of prostacyclin receptor (IP receptor). In the in vivo tail-flick assay, 2a-t (dose, 0.13 mmol/kg) receiving mice showed increased pain thresholds ranging from 20.52+/-7.25% to 90.94+/-11.97%, which were significantly higher than that ranged from 12.27+/-9.56% to 17.71+/-7.00% shown by normal saline (NS) receiving mice. In the in vivo tail bleeding assay, 2a-t (dose, 1.30 mmol/kg) receiving mice gave a bleeding time ranging from 116.3+/-8.0 s to 119.6+/-7.1 s, and NS receiving mice gave a bleeding time ranging from 116.7+/-7.5s to 119.1+/-8.7s, which were at a substantially equal level. These observations imply that no bleeding risk occurred even when 10-fold dose of analgesic assay was used. In the in vitro vasorelaxation assay, it was found that when the aortic strip contracted by noradrenaline (NE, final concentration, 10(-7) M) was treated with the solution of 2a-t in NS (final concentration, 5 x 10(-3) M) only lower percentage inhibitions ranged from 6.63+/-2.72% to 46.28+/-2.63% were recorded. Relatively higher concentration of 2a-t (5 x 10(-3) M) and relatively lower percentage inhibitions (13 of 20 less than 23.27+/-3.47%) suggest that 2a-t exhibit few vasodilation activity. To shed some light on the potential analgesic mechanisms of 2a-t, moreover, a QSAR analysis was carried out by using the multiple linear regression method. Taken altogether, the current study confirms that as selective antagonist of IP receptor 1-hydroxyl-2-substituted phenyl-4,4,5,5-tetramethylimidazoline may be a promising lead compound of analgesic agent without cardiovascular and bleeding side effects.

Rhinitis medicamentosa.

Rhinitis medicamentosa (RM) is a condition induced by overuse of nasal decongestants. The term RM, also called rebound or chemical rhinitis, is also used to describe the adverse nasal congestion that develops after using medications other than topical decongestants. Such medications include oral beta-adrenoceptor antagonists, antipsychotics, oral contraceptives, and antihypertensives. However, there are differences in the mechanism through which congestion is caused by topical nasal decongestants and oral medications. Very few prospective studies of RM have been performed and most of the knowledge about the condition comes from case reports and histologic studies. Histologic changes consistent with RM include nasociliary loss, squamous cell metaplasia, epithelial edema, epithelial cell denudation, goblet cell hyperplasia, increased expression of the epidermal growth factor receptor, and inflammatory cell infiltration. Since the cumulative dose of nasal decongestants or time period needed to initiate RM has not been conclusively determined, these medications should only be used for the shortest period necessary. Validated criteria need to be developed for better diagnosis of the condition. Stopping the nasal decongestant is the first-line treatment for RM. If necessary, intranasal glucocorticosteroids should be used to speed recovery.