Skip to main content

Advertisement

Log in

The trace amine theory of spontaneous hypertension as induced by classic monoamine oxidase inhibitors

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

The classic monoamine oxidase inhibitors (MAOIs) tranylcypromine (TCP) and phenelzine (PLZ) are powerful antidepressants that come with an equally powerful stigma, and are thus rarely prescribed—despite their well-established effectiveness. Some of these preconceptions appear to stem from unclarity, as the etiology of a rare but important side effect, ‘spontaneous hypertension’ (SH)—a significant increase in blood pressure absent dietary tyramine ingestion—remains improperly elucidated. This paper aims at uprooting some of the stigma surrounding MAOIs by advancing the trace amine (TA) theory as the causative underpinning of SH. This theory posits that SH results from the considerable influx of TAs observed following TCP- or PLZ-administration. TAs are known, albeit at greatly supraphysiological levels, to raise blood pressure on account of their propensity to exert potent indirect sympathomimetic effects; additionally, some research posits that TAs may induce vasoconstrictive effects partly or wholly separate therefrom, which would then constitute a second hypertensive mechanism. TAs are endogenous to the human body in low quantities. Both TCP and PLZ cause marked elevations of 2-phenylethylamine (PEA), meta- and para-tyramine (m-/p-TYR), octopamine (OA), and tryptamine (TRYP), following both acute and (sub)chronic administration. This paper holds that TYR plays a pivotal role in causing SH, due to its strong pressor effect. Cautious treatment of SH is advised, given its typically self-limiting nature. The risk of hypotensive overshoots must be taken into account. For severe cases, this paper urges reconsideration, following suitable confirmation trials, of antipsychotics (notably risperidone) as these agents may reduce striatal p-TYR levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Availability of data and material

Not applicable.

Code availability

Not applicable.

References

Download references

Acknowledgements

The author extends his gratitude to Glen Baker for his thorough assessment and in-depth commentary on this paper, and to Ken Gillman for his wit and wisdom in discussing this paper (and all things MAOI) with me. Thanks are also due to Andy Holt and John Finberg for their instructive comments on previous drafts.

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

Not applicable.

Corresponding author

Correspondence to Vincent Van den Eynde.

Ethics declarations

Conflict of interest

None.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Van den Eynde, V. The trace amine theory of spontaneous hypertension as induced by classic monoamine oxidase inhibitors. J Neural Transm 128, 1741–1756 (2021). https://doi.org/10.1007/s00702-021-02399-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-021-02399-9

Keywords

Navigation