Guanfacine and Guanabenz are primarily agonists at which receptors?

• A. M1
• B. NN
• C. Presynaptic α1
• D. Postsynaptic α2

Answer: (C)

Guanfacine and guanabenz act mainly as agonists of the alpha-2 adrenergic receptors, with the key action occurring at presynaptic sites in the central nervous system. When these presynaptic alpha-2 receptors are stimulated on norepinephrine-releasing neurons, they reduce the release of norepinephrine. That dampens sympathetic outflow, producing calming, antihypertensive effects. They are not acting on M1 muscarinic receptors, nicotinic (NN) receptors, or alpha-1 receptors. The presynaptic location is crucial because the primary therapeutic effect comes from inhibiting norepinephrine release rather than activating other receptor types that produce different responses.