Disease relevance of cirazoline

• In spinal dogs, cirazoline (10.0 micrograms/kg i.v.) modified neither base-line heart rate nor the tachycardia evoked by an intracoronary artery infusion of norepinephrine [1].
• In contrast, pertussis toxin treatment had only a small effect on the alpha-1 adrenoceptor-mediated pressor response to cirazoline [2].
• The lack of regulation by idazoxan and cirazoline of the density of imidazoline receptors in the brain of SHR rats suggests the existence of a relevant abnormality in the adaptive process of these receptors in this genetic model of hypertension [3].
• The centrally-acting, alpha 1-adrenergic agonists St 587, cirazoline, and SKF 89748 were very effective in blocking the response to clozapine, but ineffective in antagonizing clonidine-induced hypothermia [4].
• 6. The concomitant infusion of arginine vasopressin (0.64 iu kg-1 h-1) prevented endotoxin-induced hypotension and also prevented the impairment in responsiveness to cirazoline and to BHT 933 [5].

Psychiatry related information on cirazoline

• 4. In rat tail artery, the effects (dose-response and time-response curves) of cirazoline and TL99 on intracellular Ca2+ levels in freshly dispersed single smooth muscle cells were comparable with those obtained with organ bath studies of ring preparations of artery [6].

High impact information on cirazoline

• In pithed rats (and in isolated canine saphenous vein strips) cirazoline behaved as a preferential alpha 1-adrenoceptor agonist, since its pressor (and contractile) effects were blocked selectively by the alpha 1-adrenoceptor antagonist prazosin and were relatively unaffected by the alpha 2-adrenoceptor antagonist yohimbine [7].
• The selective alpha1-agonist cirazoline was in itself without effect on cAMP levels or thermogenesis, but when added to forskolin-stimulated cells, potentiated thermogenesis, up to the norepinephrine level, without affecting cAMP [8].
• In PC-12 membranes, [125I]AZIPI photolabels a major M(r) = approximately 61,000 peptide; the photoincorporation is blocked by cirazoline, guanabenz, and amiloride but not by idazoxan (competing ligands = 10 microM) [9].
• [125I]AMIPI is structurally related to cirazoline, an imidazoline exhibiting high affinity for IGRS and the family of related imidazoline binding sites [10].
• Male Sprague-Dawley rats received either cirazoline (0, 10, 25, 50 mug/5 mul), methoxamine (0, 30, 100 mug/5 mul), or phenylephrine (0, 3, 10, 30 mug/5 mul) ICV immediately before testing [11].

Chemical compound and disease context of cirazoline

• Neither parameter was significantly changed by cirazoline; however, clonidine at the same dose as used for cirazoline produced approximately 50% inhibition of the experimental neural tachycardia [1].
• In pithed rats with a submaximal neural tachycardia, cirazoline, like phentolamine (10.0--30.0 micrograms/kg i.v.), inhibited the decrease in heart rate produced by clonidine, suggesting that it possesses alpha-2 adrenoceptor blocking properties [1].
• Propranolol blocked the isoproterenol-induced tachycardia on both days 1 and 8 but had no effect on the cirazoline vasopressor response [12].
• After the administration of carvedilol on day 8, the cirazoline vasopressor response was 2 +/- 1 mmHg and the isoproterenol-induced tachycardia was 4 +/- 3 beats/min, indicating effective alpha 1- and beta-adrenergic blockade after chronic dosing with carvedilol [12].

Biological context of cirazoline

• LC20 phosphorylation and both phases of the contractile response to 0.3 microM cirazoline were inhibited by the myosin light-chain kinase inhibitor ML-9 (30 microM) [13].
• Piloerection was induced by cirazoline via either route of administration, and by IP methoxamine and phenylephrine, but not by ICV infusion of methoxamine or phenylephrine [11].
• After pretreatment with reserpine, nitrendipine antagonized both the B-HT 920-mediated vasoconstriction (by an average of 40 and 57%, respectively) and the cirazoline alpha-1-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• Intravenous pretreatment of the animals with cirazoline, amidephrine or St 587 diminished the heart rate response to sympathetic stimulation significantly [15].
• Cirazoline markedly reduced the proportion of the cardiac output received by the kidneys and absolute flow in these organs was only 1.4% of control after the higher dose of this agonist but flow at the lower dose was maintained by the higher cardiac output [16].

Anatomical context of cirazoline

• In normotensive Sprague-Dawley rats, repeated treatment with the imidazoline drugs idazoxan and cirazoline also increased (33-37%) the density of imidazoline receptors in the cerebral cortex [17].
• Muscle strips with the endothelium removed contracted in response to the alpha1-adrenoceptor agonist cirazoline, with half-maximal contraction at 0.23 microM [13].
• The nonadrenergic inhibition of the twitch response observed in the ileum with cirazoline resulted from weak anticholinergic activity (antimuscarinic) at the level of the postsynaptic effector organ and was observed only at high concentrations [18].
• The actions of cirazoline on the rat vas deferens [19].
• Cirazoline did not produce a significant depolarisation in blood vessels of either normotensive or hypertensive rats [20].

Associations of cirazoline with other chemical compounds

• Electrical stimulation (1-2 Hz), potassium chloride (50 mM), and the preferential alpha 1-adrenergic receptor agonist phenylephrine (1-100 microM) increased fractional tritium efflux, whereas methoxamine, cirazoline, and amidephrine were relatively ineffective [21].
• Further characterization of the guinea pig cerebral cortex idazoxan receptor: solubilization, distinction from the imidazole site, and demonstration of cirazoline as an idazoxan receptor-selective drug [22].
• MATERIALS AND METHODS: PPI was measured in male Sprague-Dawley rats after pretreatment with clonidine or the D2 antagonist haloperidol, and treatment with cirazoline, amphetamine, the D1/D2 agonist apomorphine, or the NMDA antagonist, phencyclidine [23].
• 5. In lateral saphenous vein responses to phenylephrine were enhanced by endothelial disruption, but without change in sensitivity: responses to UK-14304, B-HT 920 and cirazoline, which had a relatively slow speed of onset of contraction were not affected [24].
• Although cirazoline potentiated the heart rate elevated by an i.v. infusion of either norepinephrine, isoproterenol, or aminophylline, this effect was probably of hemodynamic origin [1].

Gene context of cirazoline

• The alpha(1)-adrenergic agonist cirazoline also increased CREB phosphorylation [25].
• Insulin and cirazoline were able to activate and phosphorylate p38 kinase [26].
• Other imidazol(ine)/guanidine drugs also were weak MAO inhibitors with the exception of guanabenz, 2-BFI and cirazoline on MAO-A (IC50S: 4-11 microM) and 2-benzofuranyl-2-imidazol (LSL 60101) on MAO-B (IC50: 16 microM) [27].
• The rank order of potency at the rat aorta was the same as that obtained for binding affinity at the rat clonal alpha 1d-adrenoceptor: norepinephrine > epinephrine > cirazoline > phenylephrine > oxymetazoline > A-61603 > methoxamine [28].
• We have also reviewed the literature for possible nonadrenergic actions of idazoxan and cirazoline, and we suggest that idazoxan receptors might be involved in the control of prolactin release from the pituitary [22].

Analytical, diagnostic and therapeutic context of cirazoline

• L-NAME, in concentrations up to 100 microM, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 microM, it potentiated cirazoline-induced vasoconstriction at each of the perfusion rates [29].
• Conversely, the alpha1-adrenoceptor agonist, cirazoline (0.05 mg kg-1 s.c.), the adrenergic agent modafinil (250, 350 mg kg-1 i.p.) and alpha2-adrenoceptor antagonists (RX 821002 0.01 mg kg-1 s.c., yohimbine 0.5 mg kg-1 i.p.), which increase noradrenergic transmission, induced a decrease of EEG power [30].
• In Experiment 1, intra-PVN microinjection of cirazoline (0, 3, 6, 12 and 24 nmol) suppressed food intake (ED50 = 23.4 nmol) without significant effects on water intake [31].
• Intravenous infusion of cumulative doses of cirazoline in vivo caused a dose-dependent decrease in superior mesenteric vascular conductance [32].
• Clonidine and cirazoline inhibited the inward current produced by nicotine (10 microM) as measured by the whole cell patch-clamp technique in differentiated PC-12 cells, recorded at a holding potential of -60 mV [33].

References