Apomorphine activity

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)...

Figure 7.7 Dopamine-induced rotation in the rat in which one (left) nigrostriatal dopamine pathway from the substantia nigra (SN) to the caudate putamen (CP) has been lesioned by a prior injection (14 days) of 6-hydroxydopamine. Amphetamine, an indirectly acting amine, releases DA and so can only act on the right side. Since the animal moves away from the dominating active side it induces ipsilateral rotation (i.e. towards the lesioned side). By contrast, the development of postS5maptic supersensitivity to DA on the lesioned side ensures that apomorphine, a directly acting agonist, is actually more active on that side and so the animal turns away from it (contralateral rotation)...

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). 

MDMA and MDE also produced locomotor patterns that differed significantly from other stimulants. Previous studies in rats have demonstrated that amphetamine-induced hyperactivity involves complex patterns of widely distributed locomotion with frequent directional changes (Geyer et al. 1986 Geyer et al. 1987). In contrast, similar levels of behavioral activation produced by scopolamine or apomorphine are associated with relatively smooth locomotor paths, in which the same movement patterns are frequently repeated. Other stimulants, such as caffeine or nicotine, increase the amount of locomotor activity without significantly altering its pattern (Geyer... 

RESPONSE Yes, it means that the animal is capable of moving around for apomorphine. But then it gets subtle. In people, too, there is initially a high level of activity to exhaust residual dopamine stores and then the activity goes down to a very low level. The apomorphine can reinstate some locomotion. I think the most convincing evidence is the heroin. It is not true motor activity. 

Apomorphine (Apokyn ) Activate postsynaptic D1 and D2 DA receptors Start an antiemetic for 3 days, then give apomorphine 2 mg SC injection (1 mg if outpatient) while monitoring blood pressure then increase by 1 to 2 mg every 2 or more hours usual MD is 2-6 mg 3-5 times daily for off periods... 

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). 

Asakura W., Matsumoto K, Ohta H., Watanabe H. (1992). REM sleep deprivation decreases apomorphine-induced stimulation of locomotor activity but not stereotyped behavior in mice. Gen. Pharmacol 23, 337-41. 

Gillin C., Kammen Dv., Post R. et al. (1981). What is the role of dopamine in the regulation of sleepwake activity In Corsini G., Gessa G., editors. Apomorphine and Other Dopaminomimetics. New York Raven Press, pp. 157-64. 

Apomorphine hydrochloride (44 Apokyn Bertek, 2004), is a semisynthetic derivative of opium alkaloid morphine (43) isolated from poppy (Papaver somniferum), and it has long been known for its erectile activity at the effective dose of 2-6 mg physicians discovered the effect over 100 years ago, but found the drug, at a much higher dose (ca. 200 mg), to be more suitable for poison victims as an emetic because it also causes serious nausea and vomiting. Apomorphine exerts its erectile effect at the central nervous system the drug has been found to be a non-selective dopamine agonist which activates both Di-like and D2-like... 

Sleepiness during daily activities Somnolence is commonly associated with apomorphine. 

There are also other non-monoaminergic alkaloids in some sacred plants which enhance catecholaminergic function. The white and blue water lilies, Nymphaea ampla and caerulea were employed as hallucinogens in both the Old and New worlds. These species contain apomorphine (an opiate with dopamine agonist activity), together with nuciferine and nornuciferine. 

Rots NY, De Jong J, Workel JO, Levine S, Cools AR, De Kloet ER (1996) Neonatal maternally deprived rats have as adults elevated basal pituitary-adrenal activity and enhanced susceptibility to apomorphine. J Neuroendocrinol 8 501-506 Sajdyk T, Schober D, Smiley D, Gehlert D (2002b) Neuropeptide Y-Y2 receptors mediate anxiety in the amygdala. Pharmacol Biochem Behav 71 419-423 Sajdyk TJ, Vandergriff MG, Gehlert DR (1999) Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test. Eur J Pharmacol 368 143-147... 

I Central initiator Compounds that have the main site of action in the CNS to activate neural events that result in coordinated signaling that results in the initiation of a penile erection (e.g. apomorphine)... 

Combinations of drugs have sometimes been used to take advantage of the differing onset and duration of action of the individual compounds. A rapid onset of action and a sufficient duration are important characteristics of drugs used in the treatment of ED. Vasoactive agents that are orally effective have been available for about 20 years, but sildenahl and apomorphine (buccal) have significantly improved upon the therapeutic efficacy of orally active agents. 

Aside from sildenahl, apomorphine is one of the few orally active (buccal route) pharmacological agents used in the treatment of ED. Apomorphine stimulates penile erection in both normal men and in men who are impotent. Apomorphine can be the drug of choice in patients with coexisting benign prostatic hyperplasia (BPH), coronary artery disease, and hypertension. 

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