Dopamine Agonists

[Michael Scally MD]

Duband S, Bidat C, Gaillard Y, Rochet M, Camdessanche JP, Peoc'h M. A fatal intoxication case involving ropinirole. J Forensic Leg Med 2012;19(7):422-5. ScienceDirect.com - Journal of Forensic and Legal Medicine - A fatal intoxication case involving ropinirole

Ropinirole, a specific non-ergoline dopamine D2-receptor agonist, belongs to the drugs applied in treatment of Parkinson's disease (PD) and restless legs syndrome (RLS) and acts as a D2, D3, and D4 dopamine receptor agonist with highest affinity for D3. Therapeutic ropinirole plasma levels in adults are defined between 0.4 and 6 ng/mL. This case report documents a fatal intoxication involving ropinirole. Information about lethal ropinirole concentrations is hitherto lacking in the literature and the assessed ropinirole levels of this case may present a step towards defining potentially lethal concentrations. A 37-year-old man without medical history was found dead in a converted van used as place of residence and an autopsy was performed. The pathological findings did not reveal an apparent cause of death but the toxicological analysis revealed the presence of ropinirole, paracetamol, and alcohol in the peripheral blood sample. Quantitative analysis revealed that ropinirole was present at a peripheral blood concentration of 64 ng/mL. The ropinirole concentrations determined in vitreous humor, urine and bile were respectively, 11 ng/mL, 2670 ng/mL and 826 ng/mL. Paracetamol was detected at a blood level of <2 mug/mL. Based on the autopsy findings and toxicological results, the cause of death was primarily attributed to intoxication with ropinirole in combination with alcohol.

 

[zkt]

Guy living in a van gets drunk and takes too many pills... blame it on the drug.

 

[keriheat]

Guy living in a van gets drunk and takes too many pills... blame it on the drug.

Sounds like he left with a grin on his face!

Based on the autopsy findings and toxicological results, the cause of death was primarily attributed to intoxication with ropinirole in combination with alcohol.

 

[zkt]

Sounds like he left with a grin on his face!

Yep, better than wasting away in an old folks home.
As for myself, nuthin fancy; big dose of H: sweet dreams.
But the timing is critical.
LOL

 

[zkt]

DA1/5 receptor activity and selective agonistsin hippocampus

Dopamine D1/D5 Receptors Gate the Acquisition of Novel Information through Hippocampal Long-Term Potentiation and Long-Term Depression

Abstract
Hebbian learning models require that neurons are able to both strengthen and weaken their synaptic connections. Hippocampal synaptic plasticity, in the form of long-term potentiation (LTP) and long-term depression (LTD), has been implicated in both spatial memory formation as well as novelty acquisition. In addition, the ventral tegmental area–hippocampal loop has been proposed to control the entry of information into long-term memory, whereas the dopaminergic system is believed to play an important role in information acquisition and synaptic plasticity. D1/D5 dopamine receptors are positively coupled to adenylyl cyclase and have been to modulate certain forms of synaptic plasticity, particularly in vitro. We investigated how D1/D5 dopamine receptors modify long-lasting synaptic plasticity at CA1 synapses of adult freely moving rats and found that receptor activation lowered the threshold for the induction of both LTP and LTD. Specific types of learning are associated with specific types of hippocampal synaptic plasticity. We found that object-configuration learning, facilitation of late-phase LTD by object exploration, and late-phase LTP by exploration of empty space were all prevented by D1/D5 receptor antagonism. Furthermore, receptor antagonism prevented electrically induced late-LTP, whereas receptor activation facilitated induction of both LTP and LTD by patterned electrical stimulation. These findings suggest that the dopaminergic system, acting via D1/D5 receptors, gates long-term changes in synaptic strength and that these changes are a critical factor in the acquisition of novel information.