Neuronal nicotinic receptor inhibition for treating mood disorders preliminary controlled evidence with mecamylamine

Shytle, R. Douglas; Silver, Archie A.; Sheehan, Kathy H.; Sheehan, David V.; Sanberg, Paul R.

doi:10.1002/da.10035

Cited by 70 publications

(55 citation statements)

References 14 publications

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“…When treatment conditions were analyzed as a function of psychiatric comorbidity, patients with current major depression showed the greatest mecamylamine-related improvements. 103 In summary, these preliminary findings with mecamylamine support the hypothesis that antidepressants may be efficacious, in part, through inhibition of nAChRs.…”

Section: Preliminary Clinical Findings With Mecamylaminesupporting

confidence: 55%

“…Indeed, preliminary evidence suggests that the potent centrally acting nAChR antagonist, mecamylamine (Inversine), which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. 102,103 We have previously proposed that the therapeutic effect of transdermal nicotine as an adjunct to neuroleptic treatment of Tourette's disorder 104 may involve nAChR inactivation resulting from a prolonged continuous exposure to nicotine. 105 In vitro studies with nicotine 71 and preliminary positive clinical observations with mecamylamine in the clinical treatment of TD patients, further support the receptor inactivation hypothesis.…”

Section: Preliminary Clinical Findings With Mecamylaminementioning

confidence: 99%

“…114 Third, while suggestive, the clinical data regarding the putative mood modulating effects of mecamylamine remain preliminary due to the small number of patients tested so far. 102,103 Thus, further rigorous investigation in more diverse affective disorder popu-lations is needed before definitive conclusions can be drawn. In addition, it will be important to determine if mecamylamine acts primarily as an antidepressant, mood stabilizer, or both.…”

Section: Limitationsmentioning

confidence: 99%

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Nicotinic acetylcholine receptors as targets for antidepressants

et al. 2002

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While the monoamine deficiency hypothesis of depression is still most commonly used to explain the actions of antidepressant drugs, a growing body of evidence has accumulated that is not adequately explained by the hypothesis. This article draws attention to contributions from another apparently common pharmacological property of antidepressant medications-the inhibition of nicotinic acetylcholine receptors (nAChR). Evidence is presented suggesting the hypercholinergic neurotransmission, which is associated with depressed mood states, may be mediated through excessive neuronal nicotinic receptor activation and that the therapeutic actions of many antidepressants may be, in part, mediated through inhibition of these receptors. In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders.

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Section: Preliminary Clinical Findings With Mecamylaminesupporting

confidence: 55%

Section: Preliminary Clinical Findings With Mecamylaminementioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

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Nicotinic acetylcholine receptors as targets for antidepressants

et al. 2002

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“…There is also evidence of altered central cholinergic tone (19)(20)(21)(22)(23) following trauma. The cholinergic system plays an important role in many cognitive domains, particularly memory and attention (24) and may play a role in the genesis of mood disorders, particularly depression (25). The serotonergic system is activated in TBI, with increased levels of serotonin particularly evident in areas of significant tissue damage and in association with lowered regional cerebral glucose utilization (10,(26)(27)(28).…”

Section: Relationship Of Profile Of Injury To Neurobehavioral Sequelaementioning

confidence: 99%

Neurobehavioral sequelae of traumatic brain injury: evaluation and management

2008

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Traumatic brain injury (TBI) is a universal public health problem. A recent review of epidemiological studies in Europe suggests an incidence of 235 hospitalized cases (including fatalities) per 100,000 population (1). In the US, the incidence is estimated at 150 per 100,000 population (2). Less data is available from other regions of the world, but TBI is acknowledged as a significant problem worldwide. Of note is that the incidence rates are calculated from hospitalized cases only, and do not include injured individuals who do not seek or have access to care. Thus, the actual incidence of injury is probably 3 to 4 fold larger than the quoted numbers. Most studies suggest that the incidence rates for TBI are greatest in the second and third decades of life, with a secondary increase in the elderly stemming from falls (2,3). Males are more likely to suffer a TBI than females (2,3).In developed countries, there has been a reduction in the mortality rates associated with TBI over the last several decades, generally attributed to improved systems of trauma care and improved motor vehicle safety design. Many individuals with mild traumatic brain injury and virtually all individuals who survive moderate and severe TBI are left with significant long-term neurobehavioral sequelae (4-6). Thus, the reduction in TBI-associated mortality rates (7) has led to a significant increase in the number of individuals with long-term neurobehavioral disorders related to TBI (8,9).Brain trauma can be caused in a number of ways, including mechanisms which penetrate the substance of the brain (e.g., projectiles) and those that do not. This paper focuses on non-penetrating injuries. Despite different contexts and instruments, the physics and biomechanics underlying damage to the brain from non-penetrating injuries have some common features. This results in certain brain regions being at greater risk for damage than others and allows for some general statements to be made about typical profiles of brain injury associated with trauma. The assessment and treatment of the neurobehavioral sequelae of TBI follow logically from an understanding of this injury profile. RELATIONSHIP OF PROFILE OF INJURY TO NEUROBEHAVIORAL SEQUELAEThere are two broad categories of forces that result in brain injury: contact (or impact) and inertial (acceleration or deceleration). Contact injuries result from the brain coming into contact with an object (which might include the skull, or some external object). Contact mechanisms often result in damage to scalp, skull, and brain surface (e.g., contusions, lacerations, hematomas) (10). Frequent sites of such injury are the anterior temporal poles, lateral and inferior temporal cortices, frontal poles, and orbital frontal cortices.Inertial injury results from rapid acceleration or deceleration of the brain that produces shear, tensile, and compression forces. These forces have maximum impact on axons and blood vessels, resulting in axonal injury, tissue tears, and intracerebral hematomas. These mechanisms also produc...

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“…9 Potential indications currently under investigation include treatment of cocaine 10 and ethanol abuse, 11 to facilitate smoking cessation, [12][13][14][15] and to treat various neuropsychiatric disorders including anxiety, 16 epilepsy, 17,18 Tourette's disorder, 19 bipolar disorder 20 and major depression. 21,22 Mecamylamine also appears to be well suited for the prophylactic treatment of autonomic dysreflexia. 23,24 The purpose of this paper is to critically review the research available regarding the possible use of mecamylamine as an aid to smoking cessation and to propose testable hypotheses that could be studied in recalcitrant smokers with mild to moderate hypertension.…”

Section: Journal Of Human Hypertensionmentioning

confidence: 99%

Mecamylamine (Inversine®): an old antihypertensive with new research directions

et al. 2002

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Mecamylamine (Inversine  ), the first orally available antihypertensive agent, is now rarely used. Although celebrated in the 1950s, mecamylamine fell out of favour because of its widespread ganglionic side effects at antihypertensive doses (30-90 mg/day). However, recent studies suggest that mecamylamine is very effective at relatively low doses (2.5-5 mg b.i.d.) for blocking the physiological effects of nicotine and improving abstinence rates in smoking cessation studies, particularly for women. When these lower doses of mecamylamine are given, patients do not experience the severity of side effects that made the drug unpopular for the

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Neuronal nicotinic receptor inhibition for treating mood disorders preliminary controlled evidence with mecamylamine

Cited by 70 publications

References 14 publications

Nicotinic acetylcholine receptors as targets for antidepressants

Nicotinic acetylcholine receptors as targets for antidepressants

Neurobehavioral sequelae of traumatic brain injury: evaluation and management

Mecamylamine (Inversine®): an old antihypertensive with new research directions

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