I heard some people actually died of the use of nmda-antagonists and I was curious what the mechanism behind this is.
I have found a study which tested how DXM affected breathing:
But DXM is a really dirty drug, so I think it is not a good case for other nmda-agonists. However an other one also points to this direction, this time for mk-801:
Another thing is that they can rise blood pressure, would they be able to cause a stroke then? But this is conflicting I found also studies, where there was a rise first in blood pressure and then it dropped again. So perhaps make your blood pressure so low the whole system collapses?
So my question is what is the mechanism of dead by an overdose of a nmda-antagonist? And also can they be lethal in normal dosages? (besides the dangerous behaviour they can induce)
I have found a study which tested how DXM affected breathing:
We investigated effects of dextromethophan (DXM), an NMDA receptor antagonist, on ventilation and metabolism in unanesthetized male and female weanling rats, and densities of neurons positive for the NR1 subunit in four medullary nuclei. Relative to saline, DXM treatment decreased oxygen consumption 12% in males and increased it 9% in females (interaction, P<0.05). DXM compared to saline decreased frequency of breathing significantly more in females than males when exposed to hypercapnia. During hypoxia, DXM relative to saline significantly decreased frequency and minute ventilation in males and increased these variables in females. NR1 positive neuron densities were significantly greater in females than males in the nucleus tractus solitarius (NTS), commissural nucleus of the NTS and hypoglossal nucleus due to higher counts. Few sex differences were noted in the dorsal vagal motor nucleus. Thus, in weanling rats NMDA receptor modulation of breathing is sex specific, as are the densities of NR1 positive neurons in medullary nuclei associated with control of breathing.
But DXM is a really dirty drug, so I think it is not a good case for other nmda-agonists. However an other one also points to this direction, this time for mk-801:
But that is in cats, not sure if that is applicable to humans. I couldn't find a lot of references, partly because these substances are actually researched in scenarios where people are hypoxic or have had a stroke. I also don't know how to interpret these articles, I have not studied pharmacology.The aim of our study was to determine the role of excitatory amino acids in controlling cardiorespiratory activity. For this purpose we administered an antagonist of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors (kynurenic acid), and an antagonist of the NMDA receptor complex (dizocilpine, more commonly known as MK-801) i.v. to chloralose-anesthetized cats while monitoring tracheal air flow, tidal volume, respiratory rate, inspiratory and expiratory durations, end tidal CO2, arterial blood pressure and heart rate. Administration of kynurenic acid in doses of 350 and 500 mg/kg produced respiratory depression as reflected by decreases in respiratory minute volume and increases in end tidal CO2. Inspiratory duration was increased with both doses and apnea (occurring during expiration) was observed with the high dose. Apnea was preceded by an apneustic pattern of breathing. Both doses resulted in an increase in blood pressure and, with the high dose, a later decrease in blood pressure was noted. Dizocilpine in doses ranging from 0.03 to 1 mg/kg produced dose-related decreases in respiratory minute volume, and increases in end tidal CO2. In addition, dizocilpine produced increases in inspiratory duration, an apneustic pattern of breathing and apnea (occurring during inspiration). Effects on blood pressure were similar to those observed with kynurenic acid. It is concluded that blockade of excitatory amino acid receptors results in pronounced effects on cardiorespiratory activity.
Another thing is that they can rise blood pressure, would they be able to cause a stroke then? But this is conflicting I found also studies, where there was a rise first in blood pressure and then it dropped again. So perhaps make your blood pressure so low the whole system collapses?
So my question is what is the mechanism of dead by an overdose of a nmda-antagonist? And also can they be lethal in normal dosages? (besides the dangerous behaviour they can induce)