Ca channel blockers & dissociative relation

[dopamimetic]

NMDA receptor complex contains a calcium channel which mediates glutamatergic excitation and excitotoxity as far as I understand. As different kinds of calcium channels exist, well the voltage gated alpha2delta target of gabapentinoids is the only one I know for sure, do different types of NMDA receptors exist (they have quite a few subunits but don't know what differentiates them) and are there a2d nmdar's?

Ca channel blockers are used to lower blood pressure and as they only talk about muscle and heart cells I guess they are peripherally selective. Yet we have things like amitriptyline, bad example that's very nonselective, which are centrally acting ones - this implies that they (among other effects) kind of antagonize Nmdar's, doesn't it? Afaik some tricyclics indeed are used for things like neuropathic pain.

 

[Deleted member 170540]

Ca channel blockers are used to lower blood pressure and as they only talk about muscle and heart cells I guess they are peripherally selective. Yet we have things like amitriptyline, bad example that's very nonselective, which are centrally acting ones - this implies that they (among other effects) kind of antagonize Nmdar's, doesn't it? Afaik some tricyclics indeed are used for things like neuropathic pain.

Several of those blood pressure meds have a CNS interaction with mu-opioids.

Potentiation of acute opioid-induced respiratory depression and reversal of tolerance by the calcium antagonist nimodipine in awake rats - Naunyn-Schmiedeberg's Archives of Pharmacology

The interaction between sufentanil, a μ-opioid agonist, and the Ca2+ antagonist nimodipine on respiration and on the development of opioid tolerance in awake rats has been analyzed. Our previous work demonstrated that chronic treatment with nimodipine together with sufentanil increases the...

link.springer.com

The interaction between sufentanil, a μ-opioid agonist, and the Ca2+ antagonist nimodipine on respiration and on the development of opioid tolerance in awake rats has been analyzed. Our previous work demonstrated that chronic treatment with nimodipine together with sufentanil increases the analgesic potency of the opioid 50 fold. Therefore, we have investigated whether the opioid-induced respiratory depression is potentiated in parallel with the analgesia. Ventilation was measured by the whole body plethysmographic method. In naive rats, sufentanil (10–80 μg/kg) consistently induced a dose-dependent respiratory depression. Pretreatment with nimodipine (200 μg/kg) potentiated this effect but to a lesser extent than it potentiated analgesia. After chronic administration of the opioid (2 μg/h, 7 days) tolerance was manifested as a reduction in both the area under the time course curve and in the maximum effect. Nimodipine (1 μg/h) administered concurrently with sufentanil for 7 days counteracted the tolerance to respiratory depression but no additional potentiation was observed. These results demonstrate that the interaction between nimodipine and sufentanil is not limited to antinociception but also exends to respiratory depression. However, compared with analgesia, the clinical relevance of a potential increase in opioid-induced respiratory depression by nimodipine may be negligible.

 

[sekio]

I don't think people include NMDA receptors when they are discussing Ca channels.

Functional NMDA receptors are heterotetramers composed of two GluN1 and typically two GluN2 subunits. There is one GluN1, four GluN2, and two GluN3 subunit encoding genes, and each gene may produce more than one splice variant.

The alpha2delta Ca channel protien is only one component of the voltage gated Ca receptor complex, so sayeth Wiki: Calcium channels [...] consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. It's analogous to the GABA-A receptor - the whole receptor is made of 5 subunits that each have different binding sites for specific drugs.

 

[Deleted member 170540]

Calcium channel blockers can also partially cancel the effects of dissociatives.

Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists - PubMed

Ketamine blocks the calcium channel associated with N-methyl-D-aspartate (NMDA) glutamate receptors. It has transient behavioral effects in healthy humans that resemble aspects of schizophrenia, dissociative disorders, and ethanol intoxication. Ethanol is an antagonist of both NMDA receptors and...

pubmed.ncbi.nlm.nih.gov

Effects of calcium channel blockers on behaviors induced by the N-methyl-D-aspartate receptor antagonist, dizocilpine, in rats - PubMed

The present study assessed the ability of voltage-sensitive calcium channel (VSCC) blockers to affect the behavioral effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine, in male Wistar rats. Dizocilpine produced dose-dependent increases in locomotor...

pubmed.ncbi.nlm.nih.gov