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Desmopressin

Desmopressin (trade names: DDAVP, Stimate, Minirin) is a synthetic replacement for antidiuretic hormone, the hormone that reduces urine production during sleep. It may be taken nasally, intravenously, or as a pill. Doctors prescribe Desmopressin most frequently for treatment of diabetes insipidus or bedwetting.

In December 2007, US drug regulators banned using desmopressin nasal sprays for treating bedwetting, but said that desmopressin pills are still a safe bedwetting treatment for otherwise healthy patients. The regulators reviewed the drug after two patients using desmopressin nasal sprays died from hyponatremia, an imbalance of sodium levels in the body.

Chemistry

Desmopressin (1-desamino-8-D-arginine vasopressin) is a modified form of the normal human hormone arginine vasopressin, a peptide containing nine amino acids.

Compared to vasopressin, desmopressin's first amino acid has been deaminated, and the arginine at the eighth position is in the dextro rather than the levo form (see stereochemistry).

Mode of action

Desmopressin works by limiting the amount of water that is eliminated in the urine.

Desmopressin binds to V2 receptors in renal collecting ducts, increasing water resorption. It also stimulates release of factor VIII from endothelial cells due to stimulation of the V1a receptor.

Desmopressin is degraded more slowly than recombinant vasopressin, and requires less frequent administration. In addition, it has little effect on blood pressure, while vasopressin may cause arterial hypertension.

Bedwetting Treatment

Doctors prescribe desmopressin frequently for treatment of bedwetting.It is usually in the form of Desmopressin acetate, DDAVP. Patients taking DDAVP are 4.5 times more likely to stay dry than those taking a placebo. The drug replaces the antidiuretic hormone for a single night with no cumulative effect.

US drug regulators banned treating bedwetting with desmopressin nasal sprays after two patients died and 59 other patients suffered seizures. The patients were using desmopressin when they developed Hyponatremia, an imbalance of the body's sodium levels.

FDA regulators said that desmopressin pills could still be considered safe for bedwetting treatment, as long as the patient was otherwise healthy. Patients must stop taking desmopressin if they become sick and have severe vomiting and diarrhea, fever, the flu, or severe cold. They should also be very cautious during hot weather or following strenuous exercise that may make them thirsty.

This is because desmopressin works by limiting the amount of water that is eliminated in the urine. A healthy body needs to maintain a balance of water and salt (sodium). If sodium levels become too low (hyponatremia) - either as a result or increased water take-up or reduced salt levels - a person may have seizures and, in extreme cases, may die.

Other Uses

Desmopressin is also used to reduce urine production in central diabetes insipidus patients and to promote the release of von Willebrand factor and factor VIII in patients with coagulation disorders such as type I von Willebrand disease, mild hemophilia A, and thrombocytopenia. Desmopressin is not effective in the treatment of hemophilia B or severe hemophilia A.

It is considered one of the best nootropics available from enhancing memory in healthy young and old adults.

Vasopressin In Healthy Young and Older Adults

Psychoneuroendocrinology 1997 Aug;22(6):387-96 Verbal memory after 3 months of intranasal vasopressin in healthy old humans. Perras B, Droste C, Born J, Fehm HL, Pietrowsky R. Department of Clinical Neuroendocrinology, University of Lubeck, Germany.

In animals, evidence has been accumulated that vasopressin (VP) improves learning and memory. In humans, this effect was not consistently demonstrated, and attempts to restore age-related memory deficits by VP also remained inconsistent. Assuming that in old subjects a beneficial effect on memory occurs only after prolonged treatment with VP, we conducted a study in 26 healthy elderly persons receiving 40 IU of VP for 3 months through the intranasal route. The trial was randomized, placebo-controlled and held double-blind. Memory was assessed by the Auditory Verbal Learning Test (AVLT) requiring the subject to learn repeatedly presented lists of 15 words. Results demonstrated no general effect of long-term treatment with VP on memory in aged humans. However, recall of an interfering word list was improved, indicating a diminished proactive interference by the peptide. Additionally, VP influenced recall depending on the serial position of an item: it improved the primacy effect (i.e. recall of the first words of a list) and impaired the recency effect. This result may indicate an improved semantic encoding (i.e. a primary effect on processes of attention) after long-term administration of VP.

Peptides 1995;16(2):179-86 Effect of acute and chronic treatment with desglycinamide-[Arg8]vasopressin in young male and female volunteers. Bruins J, Hijman R, Van Ree JM. Department of Pharmacology, Rudolf Magnus Institute, Utrecht, The Netherlands.

A single dose of DGAVP (2 mg) and a chronic treatment of 2 weeks (1 mg/day) were given to male and female volunteers by the intranasal route. Memory, mood, vigilance, and attention were tested starting 60 min after treatment. Initial storage of abstract words was improved in the males but not in the females after chronic treatment with DGAVP. This effect persisted after discontinuation of treatment. Initial storage and learning of concrete words were not affected by treatment with DGAVP. Chronic, but not acute, treatment with DGAVP reduced the reaction time for scanning of digits in a memory comparison task (Sternberg paradigm) in both sexes. No treatment effects were found for visual memory, vigilance, attention, mood, or blood pressure. The present study indicates a sexual dimorphism in the effect of DGAVP on certain memory processes.

Peptides 1992 May-Jun;13(3):461-8 Effect of a single dose of des-glycinamide-[Arg8]vasopressin or oxytocin on cognitive processes in young healthy subjects. Bruins J, Hijman R, Van Ree JM. Department of Psychiatry, Utrecht, The Netherlands.

A single dose of des-glycinamide-[Arg8]vasopressin (DGAVP, 2 mg intranasal) or oxytocin (OXT, 20 IU intranasal) was given to female and male volunteers, respectively, in a placebo-controlled double-blind trial. Memory, vigilance, attention, and mood were tested starting 10 minutes after treatment. The DGAVP dose improved delayed recognition of abstract words when measured 1 week after treatment and reduced the intercept of a memory comparison task (Sternberg paradigm). A trend was present for DGAVP and OXT to affect learning, i.e., storage processes of verbal memory in an opposite way; DGAVP improved, while OXT attenuated initial storage and the rate of storage. No treatment effects on visual memory and vigilance were found. Of the mood measures, vigor was reduced immediately after treatment with OXT.

Neuropsychobiology 1990;23(2):82-8 Influence of desglycinamide-(arg8) vasopressin on memory in healthy subjects. Bruins J, Kumar A, Schneider-Helmert D. Department of Psychology, University of Amsterdam, The Netherlands.

In 12 healthy student volunteers the influence on memory, attention and mood of a single dose of 2 mg of the vasopressin analog, desglycinamide-(arg8) vasopressin (DGAVP), given by the nasal route was investigated. On day 1 all subjects received placebo (single-blind), 1 week later they were given either DGAVP or placebo (double-blind). Memory effects were measured with the Buschke restrictive reminding method. DGAVP significantly improved storage processes, with retrieval processes less affected. Attention and mood processes were not influenced. It is suggested that DGAVP has an influence on memory processes.

Peptides 1988 Nov-Dec;9(6):1361-6 Effects of DGAVP on verbal memory. Pietrowsky R, Fehm-Wolfsdorf G, Born J, Fehm HL. Angewandte Physiologie and Innere Medizin I, Universitat Ulm, FRG.

Effects of DGAVP (desglycinamide-arginine-vasopressin, a synthetic vasopressin analog) on verbal memory were investigated in 13 healthy male volunteers. Ten word lists, each consisting of 15 words, were presented to the subjects who had to recall them according to a free recall paradigm. The total number of recalled words was not different between DGAVP and placebo treatment; but DGAVP had an effect on memory performance depending on the serial position of the words. It attenuated the primacy effect and enhanced the recency effect of memory performance. The pattern of changes after DGAVP may be consistent with an effect of the peptide on general arousal. Since the experiment was not designed to test influences of DGAVP on arousal, these considerations remain tentative.

Psychopharmacology (Berl) 1987;92(2):224-8 Does DGAVP influence memory, attention and mood in young healthy men? Snel J, Taylor J, Wegman M.

The influence of an increasing dose of the vasopressin-like peptide DGAVP (desglycinamide-arginine-vasopressin) on memory was investigated in 2 groups of 10 healthy male volunteers to provide information about the hypothesis of improvement of memory by vasopressin. At the same time we evaluated the effect of DGAVP on mood, alertness or sleepiness in a double-blind placebo-control design. The treatment group received at 9.15 a.m. intranasally a daily increasing dose from 0.1 mg at day 1 to 10.0 mg at day 5. DGAVP did not significantly affect any measure of memory or alertness. DGAVP did, however, produce a significant increase in concentration level and mood. The results of the present study provide no support for the vasopressin theory of memory improvement; rather, the results direct the attention-to-attention modulating effects.

Peptides 1984 Jul-Aug;5(4):819-22 Vasopressin analog (DDAVP) improves memory in human males. Beckwith BE, Till RE, Schneider V.

One specific analog of arginine vasopressin, 1-desamine-8-D-arginine vasopressin (DDAVP), has been shown to improve learning and memory in humans. Healthy young male adult subjects treated with DDAVP demonstrated better memory for implicational sentences than did control subjects. The same treatment had no influence on women given the same memory task. These results suggest that DDAVP may have a sexually dimorphic effect on learning and memory.

Psychiatry Res 1984 Jan;11(1):49-59 The effect of vasopressin on memory in the healthy elderly. Nebes RD, Reynolds CF 3rd, Horn LC.

The effect that vasopressin has upon memory in young and old males was tested in a double-blind crossover study. There were two 1-week medication periods; during one, subjects received 60 micrograms of vasopressin daily; during the other, placebo. Reaction time tasks were used to measure their speed of retrieval from: short-term memory (STM), long-term memory (LTM), and semantic memory (SM). While vasopressin did not affect SM retrieval time or simple vocal reaction time, it did reduce memory comparison time and perceptual-motor time in STM and retrieval time in LTM. The degree of facilitation was similar in young and old.

Peptides 1983 Sep-Oct;4(5):707-9 Vasopressin analog influences the performance of males on a reaction time task. Beckwith BE, Couk DI, Till TS.

The effects of desmopressin acetate (DDAVP), a vasopressin analogue, were investigated using the Sternberg Item Recognition Task. This task requires a subject to memorize a target set of up to four digits and then quickly to decide whether or not a given probe was in the original memory set. 15 college aged males were used as subjects in this study. Subjects received, in a double blind procedure, 0.6 ml of DDAVP (60 micrograms) or an equal volume of vehicle solution during the first test session. One week later, during the second test session, the hormone-placebo treatments were reversed. The results indicated significant main effects for set size and decision type and an interaction between treatment and session. Treatment with DDAVP during the second but not the first session improved performance at each set size as compared to treatment with the vehicle. These results indicate that DDAVP, combined with experience on this task, improved attentional processes but did not influence memory, which would have been indicated by an interaction between treatment and size of memory set.

Vasopressin in Children with Learning Disorders

Isr J Med Sci 1987 Jan-Feb;23(1-2):12-8 Animal and clinical studies of vasopressin effects on learning and memory. Hamburger-Bar R, Eisenberg J, Belmaker RH.

Cognitive deficits of attention deficit disorder in childhood are poorly responsive to presently available medication. Vasopressin derivatives have been reported to enhance learning and memory in animals and in normal humans in controlled studies. This study reports on the effects of vasopressin on learning in rats and in children with learning disorders. Vasopressin treatment 3 times weekly for 6 weeks in rats appeared to be more effective in enhancing learning and retarding extinction than did vasopressin treatment given only at the beginning of learning and again at the start of extinction. These effects were also shown to be affected by pharmacogenetic factors; since in six inbred mouse strains some showed retarded extinction with vasopressin and others did not. In 17 children with attention and learning disorders, vasopressin derivative was given daily for 10 days and compared with 10 days of placebo treatment in a randomized, crossover, double-blind design. Story memory plus position learning were significantly improved by vasopressin derivative compared with placebo. The same trend of improvement was observed in 9 Down's syndrome patients. In 15 other children with attention & learning disorders, a single dose of vasopressin derivative was compared with placebo in a randomized, crossover, double-blind design, and no benefit was found. These parallel animal & human studies suggest that repeated, but not single-dose, vasopressin treatment may benefit childhood learning disorders.

Journal of Clinical Psychopharmacology, 1999, Vol 19, Iss 1, pp 28-36 Vasopressin improves age-related sleep disturbances

Disturbed sleep is common in the elderly and is characterized by reduced time spent in slow wave sleep (SWS) and in rapid eye movement (REM) sleep. At present, no treatments are available to fully compensate for these disorders. In the elderly, vasopressin content is decreased at various brain sites. Investigating the effects of a 3-month intranasal The hormone, Vasopressin was administered for 3 months in two elderly subjects in a foregoing pilot study which observed sleep and cognitive functions. Researchers found that the most pronounced influence of the hormone was a marked increase in SWS. Daily intranasal vasopressin treatment consisted of 20 IUs before bedtime and after awakening given to 26 healthy elderly subjects (mean age, 74.2 years). Intranasal treatment of vasopressin increased (1) the total sleep time, on average, by 45 minutes; (2) time spent in SWS by 21 minutes; and (3) time in REM sleep in the second half of the night by 10 minutes. Results suggest that age-related deterioration of sleep architecture can benefit from intranasal treatment with vasopressin.

Vasopressin in Schizophrenia

Neuropsychobiology. 1989;20(3):113-9 Vasopressin (DDAVP) therapy in chronic schizophrenia: effects on negative symptoms and memory.

Brambilla F, Bondiolotti GP, Maggioni M, Sciascia A, Grillo W, Sanna F, Latina A, Picotti GB Ospedale Psichiatrico Pini, Milano, Italia

10 chronic undifferentiated schizophrenics, 6 men and 4 women, aged 28-63, with 6- to 31-year histories of the disease were given DDAVP to observe the effects of this neuropeptide on the prevalent negative symptoms of their illness. Patients were maintained on neuroleptic therapy and first given a 20-day course of placebo followed by 20 days of DDAVP i.m., 4 micrograms Andreasen Scale for assessment of negative symptoms, the Brief Psychiatric Rating Scale, the NOSIE Rating Scale and the Luria-Nebraska Rating Scale were administered to monitor negative symptomatology, behavior and memory before the study began, after placebo and after DDAVP administration. Patients were also given a growth hormone-clonidine test and in addition plasma basal concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. DDAVP therapy induced a significant improvement of negative symptomatology and a trend toward improvement of short- to medium-term memory.

Side effects

Desmopressin nasal is in the FDA pregnancy category B. Drugs in this category are not expected to harm an unborn baby.

See also

References

  • Leissinger C, Becton D, Cornell C Jr, Cox Gill J. High-dose DDAVP intranasal spray (Stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A. Haemophilia 2001;7:258-66. PMID 11380629.

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