Description
Cirazoline is an α
1-adrenergic receptor (α
1-AR) agonist (K
is = 120, 960, and 660 nM for recombinant α
1A-, α
1B-, and α
1D-ARs, respectively, in CHO cell membranes). It acts as a full agonist at α
1A- and a partial agonist at α
1B- and α
1D-ARs
in vitro (EC
50s = 70.7, 79.4, and 239.8 nM, respectively). It also acts as an antagonist at α
2-ARs with a pA
2 value of 7.56 to inhibit the norepinephrine-induced twitch response in isolated pig ileum. Cirazoline (0.01-1 μg/kg) decreases blood pressure when administered
via microinjection to the nucleus reticularis lateralis (NRL) of anesthetized normotensive cats. It enhances spatial memory and reduces depressive- and anxiety-like behavior in mice when administered at a concentration of 10 mg/L in drinking water for 2-9 months. It also enhances performance in the variable delayed response task in aged rhesus monkeys at high doses of 1-10 μg/kg but impairs performance at lower doses of 0.01-1 μg/kg.
Uses
Cirazoline hydrochloride has been used to activate the α1-noradrenergic receptors and to study the inhibitory effect of neurokinin1 (NK1) antagonists on respiratory activity using the brainstem transverse slice.
Biological Activity
Selective α 1 agonist. Also available as part of the α 1 -Adrenoceptor Tocriset™ and Mixed Adrenergic Tocriset™ .
Biochem/physiol Actions
Cirazoline is a selective α1-adrenoceptor agonist and also a non-selective ligand for the imidazoline binding site. Cirazoline dereases spatial working memory performance in aged monkeys.
References
[1] KUNIKO HONE. Selectivity of the imidazoline α-adrenoceptor agonists (oxymetazoline and cirazoline) for human cloned α1-adrenoceptor subtypes[J]. British Journal of Pharmacology, 1995, 116 1: 1611-1618. DOI:
10.1111/j.1476-5381.1995.tb16381.x[2] ROBERT R. RUFFOLO JR. JAMES E W. RECEPTOR INTERACTIONS OF IMIDAZOLINES: α-ADRENOCEPTORS OF RAT AND RABBIT AORTAE DIFFERENTIATED BY RELATIVE POTENCIES, AFFINITIES AND EFFICACIES OF IMIDAZOLINE AGONISTS[J]. British Journal of Pharmacology, 1982, 77 1: 169-176. DOI:
10.1111/j.1476-5381.1982.tb09283.x[3] P BOUSQUET J S J Feldman. Central cardiovascular effects of alpha adrenergic drugs: differences between catecholamines and imidazolines.[J]. Journal of Pharmacology and Experimental Therapeutics, 1984, 230 1: 232-236.
[4] VAN A DOZE. Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity.[J]. Molecular Pharmacology, 2011, 80 4: 747-758. DOI:
10.1124/mol.111.073734[5] A.F.T. ARNSTEN J. D J. The Alpha-1 Adrenergic Agonist, Cirazoline, Impairs Spatial Working Memory Performance in Aged Monkeys[J]. Pharmacology Biochemistry and Behavior, 1997, 58 1: Pages 55-59. DOI:
10.1016/s0091-3057(96)00477-7
