DSIP

In 16 adults with chronic insomnia randomised double-blind to intravenous DSIP at 25 nmol/kg or placebo before each of three laboratory nights, polysomnography showed higher sleep efficiency and shorter sleep latency with DSIP. The investigators judged the effects weak and partly attributable to an incidental change in the placebo group, and with no other measure including subjective sleep quality changed, concluded short-term DSIP is unlikely to benefit chronic insomnia.¹³

In 14 middle-aged adults with severe chronic insomnia treated double-blind and placebo-controlled for seven successive nights, DSIP improved night sleep from the first dose and further with repeated doses, brought night-sleep efficiency and daytime rest to the levels of normal controls, and significantly increased daytime alertness and mental performance; the effects persisted into the first placebo night after treatment.¹⁴

In six healthy volunteers given DSIP as a slow morning intravenous infusion at 25 nmol/kg under a double-blind crossover design, median total sleep time in the 130 minutes after treatment rose 59% versus placebo, and the following night showed shorter sleep onset, less stage 1 and better sleep efficiency; behavioural and EEG analysis showed no sedation of the classic pharmacological kind.¹⁵

In 24 female ASA I-II surgical patients under propofol induction and isoflurane maintenance, 12 randomised to saline and 12 across intravenous DSIP boluses of 25, 50 or 100 nmol/kg, DSIP significantly increased heart rate, decreased heart rate variability and significantly altered left-right EEG symmetry; at 25 nmol/kg it reduced delta rhythm while reducing burst suppression and raising the bispectral index, which the authors read as lightening rather than deepening anaesthetic depth.¹⁶

In an observational study, 12 patients with Cushing syndrome spent 5.8 +/- 1.4% of sleep time in delta sleep versus 14.0 +/- 2.5% in 12 matched volunteers (p < 0.01), and morning plasma DSIP-like immunoreactivity was 797 +/- 57 pmol/l in 65 patients versus 1,062 +/- 99 pmol/l in 49 volunteers (p < 0.05); the amount of delta sleep correlated negatively with 08.00 h DSIP-like immunoreactivity (r = -0.43, p < 0.05), which the authors read as against causation.¹⁷

In cats given DSIP at 30 nmol/kg intraperitoneally and recorded by EEG, EMG and EOG for 10 hours, sleep decreased rather than increased relative to saline injection: light slow-wave sleep and REM sleep were reduced and REM sleep latency lengthened.¹⁸

In 107 inpatients treated with intravenous DSIP for withdrawal, 47 from alcohol and 60 from opiates, symptoms disappeared or improved markedly in 97% of opiate addicts and 87% of alcoholics on physician and nursing assessment, with anxiety slower to resolve; about 13% of the alcohol group and 22% of the opiate group did not meet evaluation requirements, and the study was uncontrolled with no placebo or comparator arm.⁸

In an uncontrolled within-subject pilot in 7 patients with migraine and vasomotor headaches, chronic tinnitus or psychogenic pain attacks, intravenous DSIP significantly lowered pain in 6 of the 7 when the treatment period was compared with each patient's own preceding baseline, alongside a significant reduction in concomitant depressive states.¹⁹

In Sprague-Dawley rats with focal stroke from intraluminal middle cerebral artery occlusion, intranasal DSIP at 120 microgram/kg applied 60 (+/- 15) minutes before occlusion and for 7 days after reperfusion significantly improved rotarod motor performance over 21 days compared with vehicle; brain infarction was smaller than in vehicle-treated animals but the difference was not statistically significant.²⁰

In rats trained on the Morris water maze and then exposed to simulated 7,620 m hypobaric hypoxia, daily intraperitoneal phosphorylated DSIP at 10 microgram/kg increased non-REM and REM sleep on telemetric recording and improved maze performance, which the authors attributed to upregulated hippocampal CREB phosphorylation; naloxone at 1 mg/kg altered navigational memory and lowered hippocampal CREB and p-CREB.¹⁰

In healthy young men, intravenous DSIP at total doses of 3 and 4 mg produced ACTH and cortisol responses to human corticotropin-releasing hormone almost identical to placebo across two conditions of five men each, and 4 mg left the meal-related midday ACTH and cortisol surge unaffected in a further 10 men, giving no support for an inhibitory role of DSIP on ACTH and cortisol secretion in man.⁹

In rats treated with chlorpromazine, morphine and pentobarbital, intravenous DSIP at 5-30 microgram/kg significantly reduced the corticosterone released in response to corticotropin-releasing factor while leaving the corticosterone response to injected adrenocorticotropic hormone unaffected, which the authors interpreted as attenuation of CRF action at the pituitary rather than the adrenal.⁷