Medetomidine or 4(5)-[alpha-methyl-2,3-dimethylbenzyl] imidazole, having the structure ##STR1## is a relatively new drug which is known to be a potent and selective alpha-2 receptor agonist. It has been identified to be useful as an antihypertensive agent (European Patent Publication No. 72615), a veterinary sedative (European Patent Publication No. 187471), and an anxiolytic (U.S. Pat. No. 4,783,477). Medetomidine, as may be inferred from its structure (I), comprises a mixture of optical isomers; the preparation, separation and purification of the dextrorotatory and levorotatory isomers has been described (see European Patent Publication No. 300652). It has also been established that the dextrorotatory isomer--"dexmedetomidine"--is the active isomer, while the 1-isomer is far less potent.
In addition to the above-cited art, the following references relate to the chemistry and pharmacology of medetomidine, its salts, and its component isomers: A. Karjalainen, Acta Chem Scand (1988) 42:537-545; E. MacDonald et al, Eur J Pharmacol (1988) 158:119-127; E. MacDonald et al, Ann Clin Res (1988) 20:298-310; R. Virtanen et al, Eur J Pharmacol (1988) 150:9-14; R. G. Vickery et al, Anaesth Analg (1988) 67:611-615; D. Stenberg et al, J Vet Pharmacol Ther (1987) 10:319-323; and M. Scheinin et al, Br J Clin Pharmacol (1987) 24:433451.
The present invention relates specifically to the administration of dexmedetomidine through the skin. Many systems have been developed and used to deliver drugs transdermally; the delivery of drugs through the skin has proved to have many advantages. Primarily, such a means of delivery is a comfortable, convenient and noninvasive way of administering drugs. The variable rates of absorption and metabolism encountered in oral treatment are avoided, and other inherent inconveniences--e.g., gastrointestinal irritation and the like--are eliminated as well. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug. Representative patents which describe transdermal drug delivery devices include U.S. Pat. Nos.: 3,598,122; 3,598,123; 3,731,683; 3,797,494; 3,854,480; 3,923,939; 3,926,188; 3,964,482; and 4,717,568.
None of the above-cited art or any other art of which applicants are aware describes a transdermal delivery device for administering dexmedetomidine. Nor does the prior art set forth data on skin permeability or therapeutic administration rates with respect to dexmedetomidine. To the best of applicants, knowledge, then, the transdermal administration of dexmedetomidine is unknown and completely unsuggested by the art.