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Berbanes: search for novel alpha-2 adrenoceptor antagonists
L G Harsing1, G Lonart, S E Vizi
1Department of Pharmacology, Postgraduate Medical School, Hungarian Academy of Sciences, Budapest.
Polish Journal of Pharmacology and Pharmacy
|November 1, 1988
Summary
Berbanes, like CH-38083, are potent alpha-2 adrenoceptor antagonists. Molecular structure dictates activity, offering selective targeting for neural processes in the central nervous system and periphery.
Area of Science:
- Pharmacology
- Neuroscience
- Medicinal Chemistry
Background:
- Berbanes and their stereoisomers exhibit alpha-2 adrenoceptor antagonist properties.
- CH-38083 (2,3-methylenedioxy-11-betahydroxyalloberbane) demonstrates high affinity and selectivity for alpha-2 adrenoceptors.
Purpose of the Study:
- To further analyze CH-38083, a potent alpha-2 adrenoceptor antagonist.
- To investigate the structure-activity relationships of berbanes for alpha-2 adrenoceptor binding.
- To characterize xylazine-sensitive and noradrenaline-sensitive alpha-2 adrenoceptors.
Main Methods:
- Structure-activity relationship (SAR) studies of berbanes.
- Characterization of alpha-2 adrenoceptors using alloberbane derivatives in rat vas deferens and guinea-pig ileum.
- Correlation studies on molecular modifications and adrenoceptor antagonist activity.
Main Results:
- Key structural features for alpha-2 adrenoceptor binding identified: aromatic ring substituents, nitrogen atom, C-11 hydroxy group, and C-12 methoxycarbonyl group.
- Evidence suggests xylazine-sensitive alpha-2 adrenoceptors in rat vas deferens and guinea-pig ileum are similar.
- Potential subtype differences between xylazine-sensitive and noradrenaline-sensitive alpha-2 adrenoceptors in guinea-pig ileum noted.
- Molecular modifications can modulate alpha-2 antagonist activity independently of alpha-1 antagonist potency.
Conclusions:
- CH-38083 is a promising compound for studying alpha-2 adrenoceptor-mediated neural processes due to its selectivity and low affinity for other receptors.
- The study provides insights into the structural requirements for berbane binding to alpha-2 adrenoceptors.
- Findings suggest potential heterogeneity within xylazine-sensitive and noradrenaline-sensitive alpha-2 adrenoceptor populations.