Apomorphine Neuroleptics

When tested on prolactin release in isolated mammatrophs of bovine anterior pituitary, apomorphine appeared a full agonist (inhibiting release) while antagonism of the inhibition of prolactin release by the neuroleptics showed a potency more similar to that for binding than for blocking cAMP production. Also the inhibition of prolactin... 

Further complicating the picture is the induction of autoreceptor supersensitivity with chronic neuroleptic administration, as well as the fact that at least one tract-the mesocortical, which projects to the prefrontal cortex-may lack such autoreceptors. Some of the authors conducted preliminary, single-dose studies with apomorphine at a dose that stimulated presynaptic DA autoreceptors that reduced synthesis and NT release, producing a measurable acute antipsychotic effect ( 9, 10). 

Misslin, Rene, Philippe Ropartz, and L. Jung. 1984. "Impairment of Responses to Novelty by Apomorphine and Its Antagonism by Neuroleptics in Mice." Psychopharmacology 82 113-17. 

Dopamine - low doses of the dopamine agonist apomorphine increase slow-wave sleep and, like other dopaminometics, cause somnolence in patients with Parkinson s disease. Conversely, dopamine autoreceptor antagonists, which enhance dopamine release, reduce both REM and non-REM sleep. Stimulants such as cocaine cause arousal by activating D2 postsynaptic receptors, effects which are blocked by most neuroleptics. 

Figure 15. One of a family of conformers of chlorpromazine fit within limits criteria for the neuroleptic receptor. Shown in two orthogonal views aligned with apomorphine (---------------). Nitrogen position indicated by arrows.

A series of novel neuroleptic agents derived from alpha-tetralone and N-arylpiperazine has been prepared. 38 Moderate activity in inhibiting amphetamine hypermobility and in producing hypothermia was found, with compound (26) being the most active. Another N-arylpiperazine analog (27) also had neuroleptic activity in antagonizing amphetamine and apomorphine stereotypy and production of catalepsy. 39... 

Tardive Dyskinesia and Dopamine Receptor Supersensitivity - Tardive dyskinesia is a major complication of long term treatment with neuroleptic drugs 24,25,26,27 it is characterized by abnormal movement of facial muscles and extremities which frequently worsen when the neuroleptic dose is lowered or terminated. Increasing the dose, however, may temporarily alleviate the symptoms. The chronic treatment of rats and mice with neuroleptics leads to an increased motor activity and enhanced sensitivity to the motor stimulant effects of apomorphine, a direct dopamine receptor agonist28 ... 

---