VPT 321: Veterinary Neuropharmacology (2+1)

Selective α- adrenergic receptor antagonists

SELECTIVE α - ADRENERGIC RECEPTOR ANTAGONIST

Quinazoline derivative

• Prazosin
  • Prazosin is extremely potent highly selective α₁ adrenoceptor blocking drug with no action on α₂ receptors. It has 1000 times more greater affinity to α₁ receptors than for α₂ receptors.
  • It decreases peripheral vascular resistance and lowers blood pressure, by relaxing both arterial and venous smooth muscle. It also decreases venous return to the heart.
  • Unlike other non-specific α- receptor blockers, prazosin does not cause reflex tachycardia. This is because prazosin decrease cardiac pre-load and also does not cause release of nor adrenaline from sympathetic nerve endings in myocardium due to its no action on the pre junctional α₂- receptors. There are minimum changes in cardiac output, renal blood flow and glomerular filtation rate.
• Clinical uses: Treatment of systemic hypertension or pulmonary hypertension.

Selective α₂-adrenoceptor antagonists

• Yohimbine
  • It is a competitive antagonist with selective action on α₂- receptors. It is an alkaloid with structural resemblance to reserpine obtained from Pausinystalia yohimbe.
  • Yohimbine produces a short duration competitive blockade of α2 adrenergic receptor and 5-HT receptors.
  • By blocking central α₂ –adrenergic receptors releases nor adrenaline and increases sympathetic outflow. This results in increased heart rate and blood pressure. However, as it also blocks the peripheral post-junctional α₂ receptors. It causes vasodilatation and hypotension usually predominate. The vasodilator effect of yohimbine in male genetalia causes penile erection.
  • Yohimbine crosses readily the blood brain barrier and produces central nervous excitation, motor activity, ADH release, nausea and vomiting. It also antagonizes the effects of xylazine.
• Clinical uses: Yohimbine is used to antagonize the over dosage effects of xylazine.