Apomorphine antagonism

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... 

Figure 7.5 Rate recording of the dose-dependent inhibitory effects of apomorphine (pg/kg) on the spontaneous activity of a neuron in the medial prefrontal cortex of the halothane anaesthetised rat and its antagonism by haloperidol (HAL, 0.5mg/kg). Time scale is 50 min intervals. Reproduced by permission from Dailey (1992)...

In other brain areas which receive a DA input, such as the nucleus accumbens and prefrontal cortex, it appears to be inhibitory and predominently D2-mediated. This is clear from Fig. 7.5 which shows inhibition by apomorphine (mixed D2, Di agonists) of the firing of neurons in the medial prefrontal cortex of the anaesthetised rat and its antagonism by the D2 antagonist haloperidol. 

Pataki et al. showed that apomorphine and bromocriptine enhanced the elevation of body temperature induced by pituitary adenylate cyclase-activating polypeptide in rats and observed that hyperthermia was antagonized by haloperidol, suggesting the involvement of the dopaminergic system (100). 

The answer is c. (Hardman, pp 932—933.) Metoclopramide antagonizes the emetic effect of apomorphine, which is mediated by a dopamine... 

H]spiperone binding test) and in vivo (catalepsy induction, and antagonism of apomorphine-induced stereotypy in rats antagonism of apomorphine-induced emesis in dogs). On the other hand, antagonism of cisplatin-induced emesis in the dog and ferret was retained. Several representative /J-keto, ji-hydroxy and / -methoxy analogues are shown in Table 7.1. 

Metoclopramide, administered at doses higher than those required to inhibit apomorphine-induced emesis, was more effective than haloperidol in antagonizing cisplatin-induced emesis in dogs [80]. This was observed despite the fact that metoclopramide was considerably weaker than haloperidol as a D2-dopamine antagonist [43]. Subsequently, antiemetic efficacy of metoclopramide administered at high doses has been reported in cancer patients... 

Blockade of (serotonin) 5-HT2 receptors No catalepsy, no marked antagonism of apomorphine... 

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. 

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). 

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... 

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... 

The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors. Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like levodopa or apomorphine that are known to increase dopamine levels or to possess dopaminelike effects. Metoclopramide also inhibits the central and peripheral effects of apomorphine and abolishes the slowing of gastric emptying caused by apomorphine. 

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