Pharmacological and clinical-pharmacological aspects of D1 and D2 receptors
In contrast to the situation in some peripheral systems, the role of D1 receptors for clinical effects or side effects of dopaminergic therapies in Parkinson’s disease is still unclear.
This is due to the lack of clinical studies with D1 agonists as well as to quite opposing results of animal neurobiochemistry and neuropharmacology depending on species, receptor state and other factors. For therapy, dopaminergic actions can be classified by the dopamine systems involved, the presence or absence of a blood-brain barrier (i.e. inhibition by domperidone) and by their evolution on chronic oral treatment: some dopaminergic effects remain unchanged, others increase or decrease with time in the same patient = ”functional tolerance / supersensitivity development“. New therapeutic strategies should involve more selective stimulation of the affected dopaminergic system (e.g. by dopamine partial agonists) or by new drug delivery systems avoiding high first-pass variations and ”yo-yoing“ of receptor stimulation as it occurs with all available dopaminergic therapies. Positive results of such a strategy are shown by continuous dopaminergic infusion.
Additional strategies involve selective inhibition of some dopaminergic side effects (e. g. by decarboxylase inhibitors, domperidone and clozapinelike drugs), but only research on events preceeding dopamine loss will help to find possibilities of arresting the progression of the disease. For early diagnosis, except PET studies only a combined strategy involving a drug challenge and a refined measurement of motor ability can be imagined.
KeywordsDopaminergic Drug Decarboxylase Inhibitor Dopaminergic Therapy Functional Tolerance Dopaminergic Effect
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- Birkmayer W, Riederer P (1985) Die Parkinson-Krankheit, 2. Aufl. Springer, Wien New YorkGoogle Scholar
- Carlsson A (1987) Monoamines of the central nervous system. A historical perspective. In: Meltzer HY (ed) Psychopharmacology, the third generation of progress. Raven Press, New York, 39–48Google Scholar
- Gessa GL (1988) Agonist and antagonist actions of lisuride on dopamine neurons: electrophysiological evidence. J Neural Transm [Suppl] 27: 201–210Google Scholar
- Horowski R (1987) Clinical neuropharmacology of DA agonists in Parkinson’s disease. Neuroscience [Suppl] 22: 107Google Scholar
- Jenner P, Boyce S, Marsden CD (1988) Receptor changes during chronic dopaminergic stimulation. J Neural Transm [Suppl] 27: 161–175Google Scholar
- Ruggieri S, Stocchi F, Antonini A., Bellantuono P, Carta A, Agnoli A (1987) Lisuride infusion in chronically treated fluctuating Parkinson’s disease: effects of continuous dopaminergic stimulation. Trends Clin Neuropharmacol 1: 55–60Google Scholar
- Wachtel H, Rettig KJ, Löschmann P-A (1988) Effect of chronic subcutaneous minipump infusion of lisuride upon locomotor activity of rats. J Neural Transm [Suppl] 27: 177–183Google Scholar