Action of MDMA (Ecstasy) and Its Metabolites on Arginine Vasopressin Release
John K. Fallon, Dhwanil Shah, Andrew T. Kicman, A. J. Hutt, John A. Henry, David J. Neep, Mary L. Forsling
Annals of the New York Academy of Sciences June 1, 2002 DOI: 10.1111/j.1749-6632.2002.tb04181.x via OpenAlex
Summary
AI-generated from the abstractMDMA (ecstasy) can cause dangerously low sodium levels by triggering inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). In eight healthy men given a low 40 mg dose of MDMA, plasma AVP rose significantly at 1, 2, and 4 hours. A negative correlation between MDMA and AVP at 1 hour suggested a metabolite might drive the increase. Testing MDMA and five of its metabolites on isolated rat hypothalamus tissue showed all compounds increased AVP release, with the major metabolite HMMA being the most potent and DHMA the least. Most compounds also enhanced AVP release in response to potassium stimulation. These in vitro results confirm that MDMA metabolites, not just the parent drug, contribute to AVP secretion.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | Healthy drug-free male volunteers |
| Intervention | MDMA |
| Dose | 40 mg |
| Duration | 24-hour study period |
| Topics | MDMA |
| Keywords | Vasopressin Metabolite Chemistry |
| Citations | 54 |
| Key finding | MDMA and its metabolites, particularly HMMA, increase arginine vasopressin release from rat hypothalamus in vitro. |
Abstract
A bstract : 3,4‐Methylenedioxymethamphetamine (MDMA) has been reported to cause hyponatraemia, which appears to result from inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). After administration of a low dose of ( R,S )‐MDMA (40 mg) to eight healthy drug‐free male volunteers, concentrations of AVP in plasma increased significantly at 1, 2, and 4 hours. Although no relation between plasma MDMA and AVP was found on an examination of the entire data set over the 24‐hour study period, a statistically significant negative correlation was observed at 1 hour. As this occurred at a time when both AVP and MDMA concentrations were rising, it was postulated that a metabolite, or metabolites, could primarily be responsible for the increase in AVP. To test this hypothesis we examined the effect of MDMA and five of its metabolites, in the dose range 0.1‐1,000 nM, on AVP release from the isolated rat hypothalamus. All compounds tested were found to increase AVP release (using 10 nM and 1,000 nM concentrations), with 4‐hydroxy‐3‐methoxymethamphetamine (HMMA), the major metabolite of MDMA, being the most potent, and 3,4‐dihydroxymethamphetamine (DHMA) the least potent. Each compound (1,000 nM), with the exception of DHMA, also enhanced the response to 40‐mM potassium stimulation. Our findings confirm that metabolites of MDMA, in addition to the parent drug, contribute to AVP secretion in vitro . Further work will demonstrate whether this is also true in vivo .