A2-Adrenergic receptor antagonists

Catechol (22) was treated with 2-chloroacrylonitrile in basic conditions Michael addition to one OH group followed by a Williamson s reaction onto the other gave the nitrile (23) which was elaborated on to idazoxan (24) Scheme 5.7.) [14, 15]. It is claimed to be one of the most potent and selective a2-adrenergic receptor antagonists [16-19], Idazoxan shows unusual differential binding to a2-adrenoreceptors of different species [20]... 

A review of human clinical studies on the prescription drug yohimbine hydrochloride indicated that the majority of studies show that the drug induces a dose-dependent, transient, moderate increase in blood pressure but has no effect on heart rate, as would be expected for a selective a2-adrenergic receptor antagonist. The elevation of blood... 

Prazosin is a selective aradrenergic receptor antagonist that, at therapeutic doses, has little activity at a2-adrenergic receptors and clinically insignificant direct vasodilating activity The drug does not cause the other effects attributed to phentolamine. Most important, it produces less tachycardia than does phentolamine and, therefore, is useful in the treatment of essential hypertension. 

More direct evidence of noradrenergic effects comes from studies using the a2 antagonist, yohimbine. a2 adrenergic receptors are known to be present on the cell bodies and terminals of norepinephrine neurons,... 

Suryanarayana S, Daunt DA, Vonzastrow M, Kobilka BK. A point mutation in the 7th hydrophobic domain of the a2 adrenergic-receptor increases its affinity for a family of P-receptor-antagonists. J Biol Chem 1991 266 15,488-15,492. 

Celiprolol (selector) is a third-generation cardioselective, receptor antagonist with weak vasodilating and bronchodilating effects attributed to partial 2 agonist activity. It may block peripheral a2-adrenergic receptors and promote NO production (see Tables 10-4 and 10-5). Celiprolol is safe and effective for hypertension and angina. 

---