3- adrenergic antagonists 3-adrenoreceptors

As mentioned in section 4.3.3, there are two kinds of a receptor in brain and peripheral tissues. The crucial experiments have shown that brain tissue prelabeled with pH]NE will release neurotransmitter upon electrical stimulation or exposure to K+. The release is reduced by the a agonist clonidine (4.42) and stimulated by the a antagonist yohimbine (4.43). Since the adrenoreceptor involved in this latter experiment plays a vital role in modulating neurotransmitter release, it must be presynaptic and located on the nerve-ending membrane. A similar selectivity has also been shown by peripheral tissues (heart, uterus), leading to the distinction of aj (postsynaptic) and (presynaptic) adrenergic receptors. There are also presynaptic [3 receptors, which show a feedback regulation opposite to that of the ttj receptors that is, their excitation by a neurotransmitter increases NE release. 

The alpha-2-adrenoreceptor antagonist yohimbine increases adrenergic activity and may provoke anxiety and panic symptoms in patients but no or only mild symptoms in healthy volunteers. Yohimbine infusions evoke intrusive symptoms, i.e. flashbacks together with significant increase of... 

Celiprolol is a potent beta -adrenergic receptor antagonist. It has intrinsic sympathomimetic action, possesses some alpha2-adrenoreceptor antagonistic properties, is a direct vasodilator, and a direct bronchodilator. Celiprolol is incompletely and variably absorbed, eliminated both in bile and urine, and has a half-life of 4 to 5 hours. Celiprolol (200 to 400 mg/day) has efficacy similar to atenolol or propranolol in reducing blood pressure and is useful in hypertensive patients with asthma or bronchitis. Furthermore, celiprolol is as effective as atenolol in treating patients with stable angina. 

Other intracorporal agents used to induce penile erections include papaverine, a drug with a relaxant effect on smooth muscle, and phentolamine, an a-adrenergic receptor blocker. Yohimbine, an a2-adrenoreceptor antagonist, enhances noradrenergic neurotransmission and may improve erectile dysfunction via adrenergic system activation. 

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]... 

Bufuralol is a nonselective (3-adrenoreceptor blocking agent of comparable potency to propranolol. It has proven to be effective in treating hypertension and is a potent nonselective p-adrenergic receptor antagonist. Similarly to the method described earlier in Scheme 57.9, an efficient chemoenzymatic synthesis of (/ )-bufuralol has been reported involving a DKR of the chlorohydrin key intermediate rac-44 (Scheme 57.10). ... 

---