Memantine Dextromethorphan

NMDA antagonists The combined use of memantine with other NMDA antagonists (amantadine, ketamine, and dextromethorphan) has not been systematically evaluated. Approach such use with caution. 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

Memantine is not a major substrate for hepatic cytochrome P450 isoenzymes and has not been shown to significantly inhibit or induce these enzymes. However, memantine is partially excreted by renal tubular secretion. Thus, concomitant use of other medications that use the same renal system (i.e., triampterene, hydrochlorothiazide, digoxin, cimetidine, ranitidine, metformin, and quinidine) may affect plasma levels of both drugs (Namenda 2005). Memantine should not be used in combination with other NMDA receptor antagonists, such as amantadine or dextromethorphan, because these combinations have not been formally studied. The clearance of memantine can be reduced when the urine is alkalinized, such as with the concomitant use of sodium bicarbonate or carbonic anhy-... 

Sang C. N., Booher S., Gilron I., Parada S., and Max M. B. (2002). Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia efficacy and dose-response trials. Anesthesiology 96 1053-1061. 

Ketamine is chemically related to other dissociative anesthetics, including dextromethorphan (DXM), found in some over-the-counter cough syrups, and nitrous oxide (often called whippets ). Ketamine also shares a close chemical kinship to the prescriptives tiletamine and memantine. Tiletamine is used in combination with zolazepam as a veterinary anesthetic under the brand names Zoletic and Telazol. 

MEMANTINE ANALGESICS-DEXTROMETHORPHAN t CNS side-effects Additive effects on NMDA receptors Avoid co-administration... 

Popik, P., Kozela, E and Danysz, W. (2000). Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice. Naunyn-Sehmied. Arch Pharmacol. 361,... 

Drugs that make the urine alkaline (e.g. sodium bicarbonate, carbonic anhydrase inhibitors) will reduce the elimination of memantine. Memantine should be used with caution with other NMDA antagonists, such as amantadine, ketamine and dextromethorphan, or concurrent use should be avoided, because of the theoretical increased risk of adverse effects. Memantine is predicted to interact with other drugs eliminated by the same renal secretion mechanism, but no important interaction was seen with glibenclamide, hydrochlorothiazide, metformin or triamterene. 

Memantine is chemically related to amantadine, and the manufacturer advises that concurrent use should be avoided or undertaken with caution because of the increased risk of adverse CNS-related drug reactions such as psychosis. Although there are no data, an increased risk is also predicted for ketamine and dextromethorphan, which are also NMDA antagonists. Avoidance of, or caution with, concurrent use is advised. 

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