Pipamperone

Medical uses

Pipamperone was developed for use as an antipsychotic in the treatment of schizophrenia.

Pipamperone might be useful as a hallucinogen antidote or "trip killer" in blocking the effects of serotonergic psychedelics like psilocybin.

Pharmacology

Pipamperone acts as an antagonist of the 5-HT2A, 5-HT2B, 5-HT2C D2, D3, D4, α1-adrenergic, and α2-adrenergic receptors. It shows much higher affinity for the 5-HT2A and D4 receptors over the D2 receptor (15-fold in the case of the D4 receptor, and even higher in the case of the 5-HT2A receptor), being regarded as "highly selective" for the former two sites at low doses. Pipamperone has low and likely insignificant affinity for the H1 and mACh receptors, as well as for other serotonin and dopamine receptors.

Pipamperone is considered to have been a forerunner to the atypical antipsychotics, if not an atypical antipsychotic itself, due to its prominent serotonin antagonism. It is also used to normalise mood and sleep patterns and has antianxiety effects in neurotic patients.

Antidepressant effects

Low-dose pipamperone (5 mg twice daily) has been found to accelerate and enhance the antidepressant effect of citalopram (40 mg once daily), in a combination (citalopram/pipamperone) referred to as PipCit (code name PNB-01).

References

References

1. Anvisa. (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
2. (31 October 1999). "Concise Dictionary of Pharmacological Agents: Properties and Synonyms". Springer Science & Business Media.
3. (14 November 2014). "The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies". Springer.
4. (February 1977). "Sleep disorders in patients with severe mental depression: double-blind placebo-controlled evaluation of the value of pipamperone (Dipiperon)". Acta Psychiatrica Scandinavica.
5. (1 July 2009). "The Creation of Psychopharmacology". Harvard University Press.
6. (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol.
7. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology.
8. (February 1996). "Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences". The Journal of Pharmacology and Experimental Therapeutics.
9. (January 2000). "The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds". European Journal of Pharmacology.
10. (6 December 2012). "Atypical Antipsychotics". Birkhäuser.
11. (December 2006). "Influence of the antipsychotic drug pipamperone on the expression of the dopamine D4 receptor". Life Sciences.
12. (October 2011). "Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response". Psychological Medicine.
13. (22 June 2000). "Neurotransmitter Receptors in Actions of Antipsychotic Medications". CRC Press.
14. (2007). "Forty years of antipsychotic Drug research--from haloperidol to paliperidone--with Dr. Paul Janssen". Arzneimittel-Forschung.
15. (1990). "[Development of new antipsychotic drugs]". Acta Psiquiatrica y Psicologica de America Latina.
16. (1990). "[Serotonin antagonism involved in the antipsychotic effect. Confirmation with ritanserine and risperidone]". L'Encéphale.
17. (2012-12-06). "Psychotropic Agents: Part I: Antipsychotics and Antidepressants". Springer Science & Business Media.
18. Bart A. Ellenbroek, Alexander R. Cools (eds.) (6 December 2012). ''Atypical Antipsychotics.'' Basel: Birkhäuser, pp. 62 f. {{ISBN. 978-3-0348-8448-8.
19. (February 2010). "Clinical trials in CNS--SMi's eighth annual conference". IDrugs.