Possible Interaction: Diazepam and Melatonin

“Following diazepam administration, serum melatonin levels observed at 2, 3, and 4 AM were significantly lower than the corresponding values following placebo (P < 0.02 at 2 and 4 AM; P < 0.03 at 3 AM [Students' paired t test]).”

“Benzodiazepines (chlordiazepoxide and diazepam ) produced a dose-dependent decrease in the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of freely moving cats.”

“Although diazepam was about 10 times more potent than either of the melatonin analogues, results show that in general these last display better anxiolytic, anticonvulsant and sedative actions than the original molecule.”

“treatment with melatonin and N-acetyl-5-HT exacerbated the impairment by diazepam.”

“However, the co-administration of melatonin (80 mg/kg) or agomelatine (20-40 mg/kg) with diazepam , at a dose (0.25 mg/kg) inactive on its own, induced an anxiolytic-like effect in the punished drinking test and the elevated plus-maze.”

“These results indicate that, although mostly devoid of anxiolytic-like action per se, melatonin and agomelatine can potentiate the anxiolytic effects of diazepam.”

“Pretreating the animals with diazepam , carbamazepine or lamotrigine enhanced the anticonvulsant effect of melatonin.”

“ DZP reduced pineal melatonin content (−40%), N-acetyltransferase activity (−70%), and plasma melatonin levels (−40%), but had no affects on pineal hydroxyindole-O-methyltransferase activity.”

“In contrast, a 10−4 M suprapharmacological concentration of DZP increased melatonin secretion of perifused pineal glands by 70%.”

“In vivo, a single acute subcutaneous administration of DZP (3 mg/kg body weight) significantly affected pineal melatonin synthesis and plasma melatonin levels, while administration of the metabolites under the same conditions did not.”

“Our results indicate that the in vivo inhibitory effect of DZP on melatonin synthesis is not due to the metabolism of DZP.”

“ Diazepam reduced the pineal melatonin content (by a factor of 2) and the activity of N-acetyltransferase (NAT) (by a factor of 3.5), as well as plasma melatonin levels (by a factor of 1.5), but had no effects on pineal hydroxyindole-O-methyltransferase activity.”

“Results: Diazepam clearly affected pineal melatonin biosynthesis and plasma melatonin levels.”

“In addition, when melatonin was given at 20 mg/kg together with diazepam and morphine, antinociceptive responses in both the first and second phase were increased.”

“ Melatonin , injected at 20 mg/kg 15 min before formalin test, significantly increased the antinociceptive response of diazepam (1 mg/kg) or morphine (5 mg/kg) in the second phase.”

“Addition of diazepam to the superfusion medium significantly increased melatonin production in the mesopic and partly in the photopic range of illumination, without showing clear effects in the dark-adapted organ.”