Systemic neurotransmitter responses to clinically approved and experimental neuropsychiatric drugs.

Neuropsychiatric disorders are the third leading cause of global disease burden. Current pharmacological treatment for these disorders is inadequate, with often insufficient efficacy and undesirable side effects. One reason for this is that the links between molecular drug action and neurobehavioral drug effects are elusive. We use a big data approach from the neurotransmitter response patterns of 258 different neuropsychiatric drugs in rats to address this question. Data from experiments comprising 110,674 rats are presented in the Syphad database [ www.syphad.org ]. Chemoinformatics analyses of the neurotransmitter responses suggest a mismatch between the current classification of neuropsychiatric drugs and spatiotemporal neurostransmitter response patterns at the systems level. In contrast, predicted drug-target interactions reflect more appropriately brain region related neurotransmitter response. In conclusion the neurobiological mechanism of neuropsychiatric drugs are not well reflected by their current classification or their chemical similarity, but can be better captured by molecular drug-target interactions.

Auditory brainstem evoked responses in insulin-dependent (ID) and non-insulin-dependent (NID) diabetic subjects with normal hearing.

Hearing impairment has been reported to be one of the late complications of diabetes mellitus (DM), and the frequency varies. Previous data suggest that auditory brainstem potentials deteriorate long before the hearing impairment appears in patients with DM. Delay in neural conductance along the auditory pathway due to DM was assessed by means of auditory brainstem response (ABR) in 43 patients with normal hearing in a controlled study. Patients were classified according to age, presence of neuropathy. metabolic control, and duration and type of DM. ABR recordings revealed that absolute latencies of waves I, III and V were prolonged significantly in the diabetic group when compared to the control group (p < 0.05). When two diabetic groups (insulin-dependent and non-insulin-dependent) were compared with each other, the difference between the latency of wave I and the inter-peak latencies of I-III, III-V and I-V was not significant (p > 0.05). However, the difference between the latencies of waves III and V in the two diabetic groups was statistically significant. The duration of diabetes, blood glucose level and age were not associated with prolonged ABR latencies (p > 0.05). Prolongation of latency of ABR in patients with DM should alert us to possible damage to the auditory nerve, and close follow-up is needed in these patients.

The renin-angiotensin-aldosterone system (RAAS) and its relation with calcium homeostasis in male obesity.

BACKGROUND: The aim of our study was to determine whether alterations of the vitamin D-endocrine system and the renin-angiotensin-aldosterone system occur in male obesity and influence each other. MATERIAL/METHODS: 32 obese male subjects and 21 age-matched healthy male subjects were enrolled in the study. The parameters measured included serum total calcium (Ca), ionized calcium, magnesium (Mg), phosphorus (P), 25-hydroxyvitamin D (25-OHD), supine and upright aldosterone and renin activity, and urinary calcium, magnesium, and phosphorus. RESULTS: Serum total Ca and ionized calcium were slightly, but not significantly lower in obese subjects compared to controls, whereas serum magnesium phosphorus and PTH levels were significantly higher in the obese subjects. Mean urinary calcium and Mg were not significantly different, while urinary P was significantly higher in obese subjects. Mean serum 25OHD was significantly lower in obese subjects. Supine and upright aldosterone and renin were unrelated to BMI or fat mass. Supine aldosterone correlated with serum total calcium, ionized calcium and supine renin activity, but not with other minerals, PTH or 25OHD, whereas upright aldosterone did not correlate with other parameters. Supine renin activity did not correlate with any parameters, whereas upright renin correlated with serum Mg and PTH. There were significant correlations between PTH and BMI or fat mass. Urinary Mg was also related to both BMI and fat mass. CONCLUSIONS: Male obesity is associated with increased serum Mg, P, PTH and urinary P and lower supine aldosterone and 25OHD, but unchanged serum and urinary Ca.