any such group leads to an almost total loss of pharmacological action; alternatively,
the resultant compound may become an antagonist.
2. The two-carbon side chain is essential for activity, although some exceptions are
known. The benzylic carbon (next to the ring) must have the R absolute configuration.
3. The alcoholic hydroxyl can be replaced only by an amino or hydroxymethyl group.
4. Small (-H, -CH 3 ) N-substituents produce α activity; larger ones (-CH(CH 3 ) 2 , aryl)
lead to β activity.
4.3.6.1 α-Adrenergic Agonists
These compounds include NE, which acts on both α and β receptors, and epinephrine,
which is more active on β receptors. As mentioned previously, catecholamines lacking
a 4–OH group, such as phenylephrine (4.47) and methoxamine (4.48), show almost
pure α 1 activity. They are both vasoconstrictors, used in treating hypotension (low blood
pressure) and nasal congestion. These drugs may also inhibit insulin release.
Clonidine (4.42) is an α 2 agonist. Therapeutically, clonidine is a central antihypertensive agent, which may perhaps act on the baroreceptor (blood pressure sensor) reflex
pathway, on cardiovascular centers in the medulla, and also peripherally. As is evident
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