Apomorphine Antipsychotics

The 5-HT3 receptor is found appropriately in mesocortical areas and while behavioural studies with their antagonists in rodents showed potential antipsychotic activity, they have proved ineffective in patients. 5-HTia agonists may be more useful. They have been found to increase the extracellular concentration of DA in the frontal cortex of rats but diminish apomorphine-induced stereotypy (striatal effect). So they could be of some benefit, especially against negative symptoms, without causing EPSPs (see Chapter 9). 

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). 

Schaffer MG, Davis JM, Tamminga CA. Apomorphine s antipsychotic activity. Arch Gen Psychiatry 1985 42 927. 

Inhibition of conditioned (but not unconditioned) avoidance behavior is one of the most predictive tests of antipsychotic action. Another is the inhibition of amphetamine- or apomorphine-induced stereotyped behavior. Other tests that may predict antipsychotic action are reduction of exploratory behavior without undue sedation, induction of a cataleptic state, inhibition of intracranial self-stimulation of reward areas, and prevention of apomorphine-induced vomiting. Most of these tests are difficult to relate to any model of clinical psychosis. 

Most antipsychotics,but also many non-an-tipsychotic drugs, reverse deficits in PPI induced by amphetamine or apomorphine (152, 153). In contrast, Dg receptor antagonists such as haloperidol fail to reverse deficits in PPI induced by PCP or dizocilpine (153-156), while such deficits are, at least in part, reversed by clozapine (156), remoxipride (157), olanzapine (158), and quetiapine (155). Risperidone fails to reverse the effect of PCP (155), but it antagonizes the disruption of PPI induced by the 5-HT2A agonist DOI (150,153). 

Sulpiride (29) has been tested as an antipsychotic agent 42,43 and is atypical in its pharmacological profile. Sulpiride does not block DA-stimulated adenylate cyclase either iri vitro or in vivo, 44 it does not produce catalepsy 45 nor antagonize amphetamine.45 Sulpiride does block apomorphine-induced emesis in dogs44 but only weakly antagonizes other effects of apomorphine,46 yet it causes an increased turnover of DA in vivo. 45... 

Cannabis and THC are known in certain circumstances to induce anxiety or panic, and Zuardi and colleagues (1982) reported that CBD antagonises anxiogenic effects of THC along with some other marijuana-like effects in healthy volunteers. At a dose of 300 mg orally it reduced anxiety in comparison with placebo in a simulated public speaking task (Zuardi et al. 1993). CBD was also found to behave like an atypical antipsychotic in the apomorphine-induced stereotypy model in rodents (Zuardi et al. 1991). In a report of a single case, CBD (in doses up to 1500 mg/day) was found to improve psychotic symptoms without toxic effects in a psychotic patient who had experienced intolerable unwanted effects with haloperidol (Zuardi et al. 1995). 

Spontaneous motility or apomorphine-induced and amphetamine-induced motility in mice were significantly reduced P < 0.005) by aqueous kava extract (62.5-250 mg/kg) and kava resin (120—250mg/kg). In addition, the two preparations produced a significant reversal (f < 0.001) of tetrabenazine-induced ptosis (Duffield etal., 1989a,b). However, the kava elfects were smaller compared to those produced by the standard antipsychotic drugs chlorpromazine and haloperidol. 

Cannabidiol Attentuated apomorphine-induced stereotypy in animal model of psychosis-similar to effect of other antipsychotic drugs. Animal study showed increased prolactin secretion similar to described antipsychotic effect. Based on observed effects, mechanism of action may be similar to atypical antipsychotics, though no data available on specific neurotransmitters involved. 

The manufacturer of APO-go specifically notes that there is a potential interaction between clozapine and apomorphine, although they say that clozapine may also be used to reduce the symptoms of neuropsychiatric complications of Parkinson s disease. See also prochlorperazine in (c) above, and Levodopa + Antipsychotics , p.683. 

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