The compounds of this invention are dopamine agonists having various degrees of intrinsic activity and are essentially free from extrapyramidal side effects. Some of the compounds are selective autoreceptor agonists, and therefore partial agonists (i.e. activate only autoreceptors versus postsynaptic D.sub.2 dopamine receptors). Efforts to induce antipsychotic activity with dopamine autoreceptor agonists have been successful (Dorsini et al., Adv. Biochem. Psychopharmacol., 16, 645-648, 1977; Tamminga et al., Science, 200, 567-568; and Tamminga et al., Archives of General Psychiatry, 43(4), 398-402, 1986.
As selective autoreceptor agonists, the invention compounds provide functional modulation of the dopamine systems of the brain without the excessive blockade of the postsynaptic dopamine receptors which have been observed to be responsible for the serious side effects frequently exhibited by agents found otherwise clinically effective for the treatment of schizophrenia. Activation of the dopamine autoreceptors results in reduced neuronal firing a well as inhibition of dopamine synthesis and release and therefore provideS a means of controlling hyperactivity of the dopaminergic systems.
The compounds of this invention were also found to have high intrinsic activity and therefore they can behave as the natural neurotransmitter, i.e., as full agonists. As such, they are useful in the treatment of diseases having abnormal concentrations of dopamine could be used as dopamine surrogates such as schizophrenia, Parkinson's disease and Tourette's syndrome. Such agents are partial agonists at the postsynaptic dopamine D.sub.2 receptor and are thereby useful in the treatment of alcohol and drug addiction.
In the Belgian patent 850,166, Ciba-Geigy discloses compounds represented by the compound of the formula below which have both .alpha. and .beta.-adrenergic properties and are useful as cardiovascular and antihypertensive agents. ##STR2##
USPTO Backgrounds
USPTO Backgrounds