Autoradiographic distribution of μ-, δ- and κ1-opioid stimulated [35S]guanylyl-5′-O-(γ-thio)-triphosphate binding in human frontal cortex and cerebellum

Platzer, Stefan; Winkler, Anett; Schadrack, Jan; Dworzak, D.; Tölle, Thomas R.; Zieglgänsberger, W.; Spanagel, Rainer

doi:10.1016/s0304-3940(00)00943-5

Cited by 22 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We believe it is mediated through pethidine's inhibitory effect on the cerebellum that caused abnormal oculomotor findings in the absence of central nervous excitation. The opioid receptors are also found in the cerebellar structure in addition to previously defined cerebral area, and the activation of μ-receptors contributes to the oculomotor dysfunction via its inhibitory effects that support our findings 10. In the cerebellum, the activated μ-receptors inhibit the release of glutamate from the parallel fibres, diminishing activation of the Purkinje cells.…”

Section: Discussionsupporting

confidence: 88%

Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine

Dai

Chu

2014

BMJ Case Reports

View full text Add to dashboard Cite

Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid-receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long-term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.

show abstract

Section: Discussionsupporting

confidence: 88%

Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine

Dai

Chu

2014

BMJ Case Reports

View full text Add to dashboard Cite

show abstract

“…All of these types of eye movement are also generated in the cerebellum. Fourth, opioid receptors are located in the cerebellum [10,11]. The fact that both pethidine and fentanyl had qualitatively similar effects indicates that they mainly influenced the opioid receptors, especially the mu-receptor.…”

Section: Discussionmentioning

confidence: 99%

Effects of intravenous opioids on eye movements in humans: possible mechanisms

Rottach¹,

Wohlgemuth²,

Dzaja

et al. 2002

Journal of Neurology

View full text Add to dashboard Cite

Oculomotor symptoms such as downbeat nystagmus can be due to side effects of drugs. We investigated the clinical effects as well as the eye movement symptoms after intravenous administration of opiates (pethidine and fentanyl). Eye movements were recorded with the magnetic search coil technique. All four normal subjects showed a transient disturbance of eye fixation with downbeat nystagmus, a range of saccadic intrusions and oscillations, including square wave jerks and saccadic pulses, lasting from 10 to 15 minutes. The gain of sinusoidal VOR and smooth pursuit was moderately decreased; in particular the vertical pursuit showed an upward velocity offset. On the basis of the clinical findings and of recent diprenorphine PET findings in humans, which detected opiod binding sites in the cerebellum and the known inhibitory action of opiates, we hypothesized that a cerebellar dysfunction occurs after opiate administration which could possibly be mediated by inhibition of the parallel fiber activation of the Purkinje cells. Furthermore, opiate binding sites in the vestibular nuclei could be responsible for the vertical vestibular tonus imbalance involved in the pathophysiolgy of downbeat nystagmus.

show abstract

“…The whole hippocampus obtained at autopsy from subjects with no evidence of neurological disease was used as control tissue since previous reports indicate that MOR mRNA, binding and agonist‐stimulated [ 35 S]GTPγS binding are preserved for several hours after death (Platzer et al,2000; González‐Maeso et al,2002; Escribá et al,2004). Hippocampus was dissected at the time of autopsy, with a postmortem interval of 3–10 h, immediately stored at −70°C and then manipulated as described below no later than 1 week after they were obtained (Table 2).…”

Section: Clinical Data Of Patients With Pharmacoresistant Mesial Tempmentioning

confidence: 99%

Mu opioid receptor mRNA expression, binding, and functional coupling to G‐proteins in human epileptic hippocampus

Cuéllar-Herrera

Velasco

et al. 2010

Hippocampus

View full text Add to dashboard Cite

Mu opioid receptors (MOR) are known to be involved in seizure activity. The main goal of the present study was to characterize the MOR mRNA expression, binding, as well as G protein activation mediated by these receptors in epileptic hippocampus of patients with pharmacoresistant mesial temporal lobe epilepsy (TLE). In contrast with autopsy samples, hippocampus obtained from patients with mesial TLE demonstrated enhanced MOR mRNA expression (116%). Saturation binding experiments revealed significantly higher (60%) B(max) values for the mesial TLE group, whereas the K(d) values were not statistically different. Although mesial TLE group demonstrated high levels of basal binding for the G proteins (136%), DAMGO-stimulated [(35)S]GTPγS binding did not demonstrate significant alterations. In conclusion, our present data provide strong evidence that the epileptic hippocampus of patients with pharmacoresistant mesial TLE presents significant alterations in MOR. Such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations.

show abstract

Autoradiographic distribution of μ-, δ- and κ1-opioid stimulated [35S]guanylyl-5′-O-(γ-thio)-triphosphate binding in human frontal cortex and cerebellum

Cited by 22 publications

References 14 publications

Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine

Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine

Effects of intravenous opioids on eye movements in humans: possible mechanisms

Mu opioid receptor mRNA expression, binding, and functional coupling to G‐proteins in human epileptic hippocampus

Contact Info

Product

Resources

About