Alpha 2 Selective Agonists

What is the key feature of alpha 2 selective agonists?

they ONLY have an imidazoline backbone

what are the indications for alpha 2 selective agonists?

• HTN

  • stimulation → inhibition of sympathetic outflow → antihypertensives

• Clonidine

  • imidazoline ring subbed at position 2

  • 2 chloro groups have selective interaction with alpha 2

    • Cl groups withdraw e-s from ring → partial (+) charge

• guanabenz

  • imidazoline ring is opened

    • makes it a guanidine backbone system

  • high affinity to alpha 2 receptors

  • lipophilic

• Guanfacine

  • guanidine backbone (same as guanabenz)

  • lipophilic

• Apraclonidine

  • amino derivative of clonidine

  • added amino group → polar and unable to cross BBB

  • indication: glaucoma

Why are alpha 2 selective agonists typically given orally?

• oral absorption avoids peripheral vasoconstriction that may result in preventing NE reuptake into the synapse