Safety of Double‐Dose Transdermal Scopolamine

Bar, Ronen; Gil, Amnon; Tal, Dror

doi:10.1592/phco.29.9.1082

Cited by 13 publications

(9 citation statements)

References 12 publications

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“…With incremental exposure, people also can develop context specific adaptations so that, for example, they can move between a rotating artificial gravity environment and a stationary environment without either sensory motor control or motion sickness problems (Graybiel and Knepton 1978a, b; Lackner and DiZio 2000a, b, 2006). Drugs such as promethazine and scopolamine provide protective benefit (Bar et al 2009; Davis et al 1993; Graybiel and Lackner 1987; Gordon et al 2001; Klocker et al 2001; Nachum et al 2001, 2006; Simmons et al 2010). These drugs are central nervous system depressants and induce drowsiness so that they are often used in combination with dexedrine and ephedrine, respectively.…”

Section: How Can Motion Sickness Be Avoided or Attenuated?mentioning

confidence: 99%

Motion sickness: more than nausea and vomiting

2014

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Motion sickness is a complex syndrome that includes many features besides nausea and vomiting. This review describes some of these factors and points out that under normal circumstances, many cases of motion sickness go unrecognized. Motion sickness can occur during exposure to physical motion, visual motion, and virtual motion, and only those without a functioning vestibular system are fully immune. The range of vulnerability in the normal population varies about 10,000 to 1. Sleep deprivation can also enhance susceptibility. Systematic studies conducted in parabolic flight have identified velocity storage of semicircular canal signals—velocity integration—as being a key factor in both space motion sickness and terrestrial motion sickness. Adaptation procedures that have been developed to increase resistance to motion sickness reduce this time constant. A fully adequate theory of motion sickness is not presently available. Limitations of two popular theories, the evolutionary and the ecological, are described. A sensory conflict theory can explain many but not all aspects of motion sickness elicitation. However, extending the theory to include conflicts related to visceral afferent feedback elicited by voluntary and passive body motion greatly expands its explanatory range. Future goals should include determining why some conflicts are provocative and others are not but instead lead to perceptual reinterpretations of ongoing body motion. The contribution of visceral afferents in relation to vestibular and cerebellar signals in evoking sickness also deserves further exploration. Substantial progress is being made in identifying the physiological mechanisms underlying the evocation of nausea, vomiting, and anxiety, and a comprehensive understanding of motion sickness may soon be attainable. Adequate anti-motion sickness drugs without adverse side effects are not yet available.

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Section: How Can Motion Sickness Be Avoided or Attenuated?mentioning

confidence: 99%

Motion sickness: more than nausea and vomiting

2014

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“…For example, the ED50 for hippocampus-independent tone fear conditioning was about 14 times higher than the ED50 for hippocampus-dependent context conditioning, even though this comparison is made off-drug and tone and context learning occurred simultaneously. Additionally, SCOP has been used in humans to treat a variety of conditions including seasickness (46), Parkinson’s disease (47) and depression (48–50). Thus, SCOP met the three characteristics we noted above, indicating it was a promising candidate for the decontextualization of extinction.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic Blockade Frees Fear Extinction from Its Contextual Dependency

Zelikowsky

Hast

Bennett

et al. 2013

Biological Psychiatry

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Background Fears that are maladaptive or inappropriate can be reduced through extinction training. However, extinction is highly context-sensitive, resulting in the renewal of fear following shifts in context, and limiting the clinical efficacy of extinction training. Lesion and inactivation studies have shown that the contextualization of extinction depends on the hippocampus. Parallel studies have found that intrahippocampal scopolamine blocks contextual fear conditioning. Importantly, this effect was replicated using a non-invasive technique in which a low dose of scopolamine was administered systemically. We aimed to transfer the effects of this non-invasive approach to block the contextualization of fear extinction. Methods Rats were tone fear conditioned and extinguished under various systemic doses of scopolamine or the saline vehicle. They were subsequently tested (off drug) for tone fear in a context that was the same (controls) or shifted (renewal group) with respect to the extinction context. Results The lowest dose of scopolamine produced a significant attenuation of fear renewal when renewal was tested either in the original training context or a novel context. The drug also slowed the rate of long-term extinction memory formation, which was readily overcome by extending extinction training. Scopolamine only gave this effect when it was administered during, but not after extinction training. Higher doses of scopolamine severely disrupted extinction learning. Conclusions We discovered that disrupting contextual processing during extinction with the cholinergic antagonist scopolamine blocked subsequent fear renewal. Low doses of scopolamine may be a clinically promising adjunct to exposure therapy by making extinction more relapse-resistant.

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“…One small randomised, crossover, double blind study in healthy young men reported on double dose hyoscine patch therapy as a potential treatment for those in whom a single patch is ineffective, and concluded that two patches were safe and well tolerated in this group. 20 Faster onset of action may be obtained through administration as a nasal spray. 21 A small randomised, placebo controlled, double blind crossover trial using experimentally induced motion sickness in young adults showed the nasal preparation to be effective, with no significant decrease in alertness.…”

Section: Antimuscarinicsmentioning

confidence: 99%