Stereochemical and pharmacological differences between naturally occurring p-synephrine and synthetic p-synephrine

p-Synephrine, the primary protoalkaloid in Citrus aurantium (bitter orange) and some other Citrus species, exists in nature in the l- or [R-(−)]-enantiomeric form, whereas synthetic p-synephrine is a racemic mixture of the l- and d-enantiomeric forms. Based on receptor binding, the synthetic form is believed to exert approximately half the pharmacological activity of the naturally occurring protoalkaloid. This difference occurs because the d- or [S-(+)]-form provides little or no binding to adrenergic receptors in contrast to the l-form. Receptor binding studies also provide an explanation for the differences in pharmacological effects between the isomers p-synephrine and m-synephrine.

► We compare the adrenoreceptor binding of the l- and d-enantiomeric forms of p-synephrine.
► We compare the adrenoreceptor binding of p-synephrine and m-synephrine.
► We discuss the effects of small stereochemical differences on adrenoreceptor binding.
► We discuss the relationship between receptor binding and pharmacological properties.