Apomorphine Antidepressants

Animal behavioral models can be used to evaluate the effect of antidepressants on depression [Thiebot et al. 1992]. If TMS and ECT exert antidepressant effects by a similar mechanism, animal models for depression that are sensitive to electroconvulsive shock [ECS] should also be sensitive to TMS. ECS has effects on known animal models for depression. These effects may be displayed after recovery from the immediate effects of the convulsions [Thiebot et al. 1992]. We evaluated the effects of TMS on the forced swimming test and on apomorphine-induced stereotypy, a sensitive behavioral measure for the effects of repeated ECS. 

Recently, a method for TMS of the brain has been developed. By using TMS it is possible to noninvasively depolarize neurons located deep in the brain without induction of seizures or pain. Thus, it may be possible to compare behavioral effects of TMS and known effects of repeated ECS and other antidepressants in rats. ECS reverses behavioral despair in the swim test and enhances apomorphine hyperactivity and stereotypy. TMS appears to have similar effects to ECS on reversal of the despair in the swim test. Rapid [25-Hz] TMS but not slow (0.2-Hz) TMS potentiated apomorphine stereotypy. ECS is followed by a postictal inhibitory period for further seizures. In this study, TMS as well as ECS increased the seizure threshold for subsequent stimulation and decreased the duration of subsequent seizure. Rapid [25-Hz] TMS but not slow [5- or 1-Hz) TMS decreases the duration of seizure induced by electrical current. 

Piribedil is a more direct DA agonist than is minaprine or CNS stimulants, lacking the effects of the former on the serotonergic and of the latter on the noradrenergic system. Like apomorphine, piribedil can stimulate presynaptic DA autoreceptors at low doses, but acts as a postsynaptic DA agonist at higher doses. Unlike apomorphine, which has pronounced emetic properties and has not been studied in depression, piribedil appeared to have modest antidepressant effects in patients with low pretreatment CSF levels of HVA and 5-HlAA and may be especially effective in those with particular poly-somnographic features [Kapur and Mann 1992]. 

Allison K, Paetsch PR, Baker GB, et al Chronic antidepressant treatment attenuates motor suppressant effects of apomorphine without changing [ H] GBR12935 binding. Eur J Pharmacol 249 125-131, 1993 Altamura C, Maes M, Dai J, et al Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Eur Neuropsycho-pharmacol 5 [suppl) 71-75, 1995... 

The hypotensive adverse effects of apomorphine may possibly be increased by alcohol. The concurrent use of other drugs used for erectile dysfunction or dopamine agonists or antagonists is not recommended. However, domperidone, and prochlorperazine are said not to interact when apomorphine is used for erectile dysfunction, and domperidone is the recommended antiemetic when apomorphine is used for Parkinson s disease. There is evidence that antidepressants, antiepileptics, and ondansetron do not interact adversely. 

The manufacturers say that no studies about interactions between apomorphine and antidepressants have been undertaken, but clinical experience in erectile dysfunction suggests that no interaction occurs. ... 

A shift to antidepressive properties iti the benzodiazepines was also described for (135). Reversal of oxotremorine-induced hypothermia, inhibition of yohimbine aggregate toxicity and potentiation of apomorphine gnawing were used as antidepressive test. Anti-anxiety activity, as measured by prolongation of hypoxic survival time, and anticonvulsive properties were, however, also quite strong [332]. 

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