The Mauve Factor of Porphyria, 3‐Ethyl‐5‐hydroxy‐4,5‐dimethyl‐delta‐3‐pyrroline‐2‐one: Effects on Behaviour of Rats and Mice

Abstract

The monopyrrole, 3-ethyl-5-hydroxy-4,5-dimethyl-delta 3-pyrroline-2-one (HPL), was given by intraperitoneal injection to rats (0.65 mmol/kg) and to mice (0.98 and 1.95 mmol/kg). Behaviour of the rats was assessed for 1.5 hr after injection by monitoring their spontaneous activity, while behaviour of the mice was examined by ethological procedures during dyadic encounters over a 5 min. period at 50-60 min. following injection. Activity of the rats, once habituated to the cage, was reduced by HPL. No other abnormalities were discernible. In mice, HPL at 1.95 mmol/kg increased the frequency of "head twitch" and evoked a smaller increase of "backward locomotion". There were no changes in overall agonistic, social or non-social behaviour in the HPL treated mice. Plasma concentrations of HPL in mice treated with the highest dose level amounted to 0.3 +/- 0.1 mmol/l, many-fold above its plasma concentrations during acute porphyric attacks in man. It thus appears that in rodents HPL has slight behavioural activity, but that it is unlikely to play any significant role in the psychiatric disturbances of acute porphyria.

Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis

“…Urinary HPL is thought to arise as an abnormal product of haeme metabolism induced by haemeoxidase under conditions of extreme oxidative stress where the porphyrin moiety of haemoglobin becomes degraded or where there is abnormal porphyrin synthesis [ 82 - 85 ]. When injected into rats and mice, HPL causes reduced activity, head twitching and backward locomotion (retreat) behaviour [ 86 ] and patients with elevated HPL levels report symptoms of anxiety, depression, low stress-tolerance and mood swings. HPL may also be stress and catecholamine-related and as such, elevated levels may be disorder-non-specific [ 87 ].…”

Clinical Test of Pyrroles: Usefulness and Association with Other Biochemical Markers

“…Increases in pyrrole levels and excretion may occur as a result of stress-induced changes in intestinal permeability, which in turn leads to increased pyrrole absorption. To the extent that pyrrole excretion may be an indicator of heme breakdown due to emotional stress, oxidative stress, or nutrient deprivation, a study of the correlation between urinary pyrroles and nutrient levels should be of interest [18,[20][21][22].…”