Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters.

BACKGROUND: Self-inflicted injury, including cutting or burning, is the most frequent reason for psychiatric visits to medical emergency departments. This behavior, particularly when there is no apparent suicidal intent, is poorly understood from both biological and clinical perspectives. OBJECTIVE: To examine the role of endogenous opioids and monoamine neurotransmitters in non-suicidal self-injury (NSSI). METHODS: We compared cerebrospinal fluid (CSF) levels of endogenous opioids, 5 hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA) in individuals with a history of repetitive non-suicidal self-injury with a diagnostically-matched group of individuals who had never engaged in non-suicidal self-injury. History of suicidal behavior, demographic background and psychopathology was assessed. All patients were diagnosed with a Cluster B personality disorder (i.e. borderline, antisocial, narcissistic or histrionic) (N=29) and had a history of at least one suicide attempt. Fourteen participants had a history of repeated non-suicidal self-injurious behavior (NSSI) in adulthood and 15 did not (no NSSI). RESULTS: The NSSI group had significantly lower levels of CSF beta-endorphin and met-enkephalin when compared with the non-NSSI group. CSF dynorphin, HVA and 5-HIAA levels did not differ. Severity of depression, hopelessness and overall psychopathology was greater in the NSSI group. CONCLUSION: beta-endorphin and met-enkephalin, opioids acting upon receptors involved in mediating stress-induced and physical pain analgesia respectively, are implicated in NSSI. Serotonergic and dopaminergic dysfunctions do not appear to be related to NSSI. Based on our findings, we propose a model of non-suicidal self-injury. Our results suggest that drugs acting on the opioid system warrant exploration as pharmacological treatments for NSSI.

Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy-2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid receptor agonists and analgesics.

In order to improve the analgesic activity and pharmacokinetics of thioureas 2 and 3, which we previously developed as potent vanilloid receptor (VR) agonists, we prepared and characterized phenolic modifications of them and of their amide surrogates (7, 8). The aminoethyl analogue of the amide template 13 was a potent analgesic with an EC50=0.96 microg/kg in the AA-induced writhing test and with better in vivo stability than the parent phenol.

3-Acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid as novel vanilloid receptor agonists.

A series of 3-acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid were designed and synthesized as vanilloid receptor agonists containing the three principal pharmacophores of resiniferatoxin. Amide analogues 23, 5 and 11 were found to be potent agonists in vanilloid receptor assay both for ligand binding and for activation.

Sensitive determination of tyrosine metabolites, p-hydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenyl-acetic acid and 4-hydroxy-3-methoxymandelic acid, by gas chromatography-negative-ion chemical-ionization mass spectrometry. Application to a stable isotope-labelled tracer experiment to investigate their metabolism in man.

A method has been established for studying the dynamic metabolism of tyrosine to its metabolites in humans using a deuterium-labelled amino acid. Phenylalanine-d5 was administered orally to human subjects (5 mg/kg) and the levels of p-hydroxyphenylacetic acid-d4, 4-hydroxy-3-methoxyphenylacetic acid-d3, and 4-hydroxy-3-methoxymandelic acid-d3 excreted into urine every hour were determined by gas chromatography-negative-ion chemical-ionization mass spectrometry. This method was also applied to some patients with depression and it was possible to detect a slight alteration in the excretion of some compounds compared with the control.