[Quinolozidinylalkylamines with antihypertensive activity].

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Cardiovascular Research

Background:

• Lupinylamine exhibits hypotensive activity due to ganglionic blocking properties.
• Steric hindrance near the basic function of ganglioplegic amines is crucial for activity.
• Existing research highlights the importance of molecular structure in drug efficacy.

Purpose of the Study:

• To synthesize and evaluate novel quinolizidine derivatives for antihypertensive properties.
• To investigate the structure-activity relationship of these compounds.
• To compare the efficacy of synthesized amines with existing antihypertensive drugs.

Main Methods:

• Synthesis of various quinolizidine derivatives, including N-substituted and epimeric forms.
• Oral administration of synthesized amines to spontaneously hypertensive rats.
• Assessment of blood pressure reduction and duration of effect.
• Evaluation of ganglionic blocking activity using the cat nictitating membrane response.

Main Results:

• Amines (II), (III), and (XI) demonstrated significant and prolonged antihypertensive effects in rats.
• Other tested compounds showed minimal or no effect on blood pressure.
• Amine (II) was found to be 2-3 times more potent than alpha-methyl-DOPA.
• Amine (II) exhibited ganglionic blocking activity, 1.2 times that of mecamylamine.

Conclusions:

• Quinolizidine derivatives, particularly amine (II), possess potent antihypertensive properties.
• The antihypertensive activity is linked to ganglionic blocking mechanisms.
• These findings suggest promising therapeutic potential for novel quinolizidine-based antihypertensives.