Even though N-t-butylnorepinephrine is more B2 selective, it suffers from a disadvantage with respect to stability. Why?
N-t-butylnorepinephrine is a catechol and can easily be hydrolyzed by COMT (short half-life).
11. Recognize the structure of Terbutaline. How is Terbutaline structurally similar to N-t- butrynorepinephrine? How is it different? The structural difference also affords greater stability to Terbutaline. Why?
Terbutaline is similar to N-t-butylnorepiniphrine in that it has a tert butyl group. But instead of being a catechol, it has a resorcinol ring (one extra carbon between hydroxyl groups). The resorcinol ring means it is NOT a catechol so it can’t be broken down by COMT (longer half-life). It is also resistant to MAO. It…show more content… It is resistant to COMT because it isn’t a catechol. Still can be metabolized by MAO (short half-life). No CNS penetration due to being polar.
15. Understand how methyldopa is converted to the active form methyl-norpinephrine, an alpha-2 agonist. Understand why methyl-norepinephrine can’t be given as a drug itself.
Methyldopa is a prodrug. It is polar, but it can get into the brain due to fooling a transporter into thinking it is tyrosine. Once it gets inside the brain, it is converted to the active form. It can’t be given as a drug because it is too polar to cross the BBB. Once the l-alpha-methyldopa is in the brain, the carboxyl group is removed to make it methyldopamine. A hydroxyl group is added to get methylNE which binds to A2 receptors. (L-alpha-methyldopa aromatic l-amino acid decarboxylase alpha-methyldopamine dopamine beta-hydroxylase 1R, 2S-alpha-methylNE)
16. Know the structural relationship between ephedrine, pseudoephedrine, amphetamine, and methamphetamine, and be able to explain the extent of CNS effects on the basis of these structural…show more content… EPI binds to B2, pseudoephedrine doesn’t.
Indirect acting sympathomimetics include amphetamine and methamphetamine. There is no receptor binding so NE is displaced by dopamine from synaptic vesicles. Amphetamine and methamphetamine don’t have hydroxyl groups so they are less polar and thus, have more CNS effects (potential for abuse)—both cause the release of neurotransmitters and replace them at junctions. Methamphetamine is more potent than amphetamine and pseudoephedrine due to being more lipophilic. There are restrictions on pseudoephedrine because all you have to do is remove the hydroxyl group to get methamphetamine.
17. Know the general structural features of beta-blockers. How are the structures of Beta-1 selective blockers different from non-selective blockers?
To fit into a beta receptor and keep a neurotransmitter from binding, we need a N with an isopropyl group to bind to the B receptor and to make the ring prevent binding of NE. So, we can replace the hydroxyl groups on a catechol with chlorine groups instead to give beta antagonistic activity (dichloroisoproterenolol or
