Applications of deuterium labelling in pharmacokinetic and concentration-effect studies of clonidine

Abstract

Clonidine 2-(2,6-dichlorophenylamino)-2-imidazoline, Catapres (Figure 4.1), is a potent hypotensive agent widely used in the treatment of patients with high blood pressure (Conolly, 1975). Data from experiments in animals suggest that the hypotensive action of clonidine is predominantly due to stimulation of alpha-adrenoceptors in the central nervous system (Kobinger, 1975), resulting in a reduction of activity in sympathetic nerves (Schmitt and Schmitt, 1969). A similar mechanism probably operates in man, since clonidine does not lower blood pressure in patients with chronic cervical spinal cord transection (Reid et al., 1977). The use of clonidine in the clinic is limited because it consistently causes dry mouth and sedation which also probably arise from the drug’s effects within the central nervous system (Rand, Rush and Wilson, 1969).