Tags

Type your tag names separated by a space and hit enter

L-DOPA potentiation of the serotonergic deficits due to a single administration of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine to rats.
Eur J Pharmacol. 1991 Oct 02; 203(1):41-9.EJ

Abstract

The role of dopamine in the serotonergic neurotoxicity of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine, methamphetamine, N-ethyl-3,4-methylenedioxyamphetamine and fenfluramine was assessed by determining the long-term effect of their coadministration with the dopamine precursor, L-DOPA (L-2,4-dihydroxyphenylalanine). L-DOPA administration potentiated the regional deficits in brain concentrations of serotonin measured one week after a single high dose of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine but did not alter the neurochemical response to N-ethyl-3,4-methylenedioxyamphetamine nor to fenfluramine. Consistent with this, in vitro release studies found the latter two agents to be the weakest of the five at increasing [3H]dopamine efflux from preloaded rat striatal slices. As an estimate of in vivo release, the effect of each agent on striatal dopamine concentrations was determined. Only those agents showing a synergism with L-DOPA in the long-term studies also produced changes in striatal dopamine consistent with an increase in transmitter release and synthesis. These results provide additional support for the hypothesis that dopamine release plays a role in the neurotoxicity of methylenedioxymethamphetamine, p-chloroamphetamine and methamphetamine. The lack of effect of L-DOPA on the neurotoxicity of fenfluramine as well as the modest effects of fenfluramine on dopamine release indicate this drug may produce its long-term effects on the serotonergic system through a unique mechanism not involving dopamine.

Authors+Show Affiliations

Marion Merrell Dow Research Institute, Cincinnati, OH 45215.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1686766

Citation

Schmidt, C J., et al. "L-DOPA Potentiation of the Serotonergic Deficits Due to a Single Administration of 3,4-methylenedioxymethamphetamine, P-chloroamphetamine or Methamphetamine to Rats." European Journal of Pharmacology, vol. 203, no. 1, 1991, pp. 41-9.
Schmidt CJ, Black CK, Taylor VL. L-DOPA potentiation of the serotonergic deficits due to a single administration of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine to rats. Eur J Pharmacol. 1991;203(1):41-9.
Schmidt, C. J., Black, C. K., & Taylor, V. L. (1991). L-DOPA potentiation of the serotonergic deficits due to a single administration of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine to rats. European Journal of Pharmacology, 203(1), 41-9.
Schmidt CJ, Black CK, Taylor VL. L-DOPA Potentiation of the Serotonergic Deficits Due to a Single Administration of 3,4-methylenedioxymethamphetamine, P-chloroamphetamine or Methamphetamine to Rats. Eur J Pharmacol. 1991 Oct 2;203(1):41-9. PubMed PMID: 1686766.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-DOPA potentiation of the serotonergic deficits due to a single administration of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine to rats. AU - Schmidt,C J, AU - Black,C K, AU - Taylor,V L, PY - 1991/10/2/pubmed PY - 1991/10/2/medline PY - 1991/10/2/entrez SP - 41 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 203 IS - 1 N2 - The role of dopamine in the serotonergic neurotoxicity of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine, methamphetamine, N-ethyl-3,4-methylenedioxyamphetamine and fenfluramine was assessed by determining the long-term effect of their coadministration with the dopamine precursor, L-DOPA (L-2,4-dihydroxyphenylalanine). L-DOPA administration potentiated the regional deficits in brain concentrations of serotonin measured one week after a single high dose of 3,4-methylenedioxymethamphetamine, p-chloroamphetamine or methamphetamine but did not alter the neurochemical response to N-ethyl-3,4-methylenedioxyamphetamine nor to fenfluramine. Consistent with this, in vitro release studies found the latter two agents to be the weakest of the five at increasing [3H]dopamine efflux from preloaded rat striatal slices. As an estimate of in vivo release, the effect of each agent on striatal dopamine concentrations was determined. Only those agents showing a synergism with L-DOPA in the long-term studies also produced changes in striatal dopamine consistent with an increase in transmitter release and synthesis. These results provide additional support for the hypothesis that dopamine release plays a role in the neurotoxicity of methylenedioxymethamphetamine, p-chloroamphetamine and methamphetamine. The lack of effect of L-DOPA on the neurotoxicity of fenfluramine as well as the modest effects of fenfluramine on dopamine release indicate this drug may produce its long-term effects on the serotonergic system through a unique mechanism not involving dopamine. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/1686766/L_DOPA_potentiation_of_the_serotonergic_deficits_due_to_a_single_administration_of_34_methylenedioxymethamphetamine_p_chloroamphetamine_or_methamphetamine_to_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0014-2999(91)90788-R DB - PRIME DP - Unbound Medicine ER -