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Stimulus-Secretion Coupling: Ions
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
The fact that an increase in Ca2+ within secretory cells is not the universal trigger in stimulus-secretion coupling was reviewed by Gomperts (1986). This topic was taken up specifically with isolated bovine chromaffin cells by Cobbold, Cheek, Cuthbertson et al. (1987) who monitored calcium transients in response to nicotine and high potassium concentration in single adrenal chromaffin cells microinjected with the photoprotein aequorin. Both agonists produced a transient (60 to 90 sec) increase in Ca2+. At certain levels, the treatment with potassium resulted in the same calcium transient as produced by certain levels of nicotine but less than one-third of the secretory response. Cobbold et al. (1987) suggested that nicotinic agonists generate an alternative second messenger in addition to the increase in Ca2+.
Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
There are two therapeutically useful nicotinic agonists for the treatment of tobacco dependence: nicotine itself, which is available in patches or gum to treat smokers’ dependence, and varenicline (Chantix®), which binds to the alpha4/beta2 nicotinic receptor and relieves the cravings and withdrawal symptoms.40 Given the fact that the neuronal nicotinic receptor is damaged by beta amyloid in Alzheimer’s disease, it is likely that we will soon see some new nicotinic drugs that are useful in treating this disorder.41
Cognitive Functions, Attention-Deficit Hyperactivity Disorders, and Alzheimer’s Disease
Published in Divya Vohora, The Third Histamine Receptor, 2008
Maria Beatrice Passani, Patrizio Blandina, Kaitlin E. Browman, Gerard B. Fox
In addition to the use of aged animals and transgenic mice, Alzheimer’s researchers have long used lesion models to try to reproduce cognitive and cholinergic deficits observed in the human disease. Cholinergic neurons within the basal forebrain nuclei are found alongside various noncholinergic neurons, and nonselective lesions of all neuron types within this area lead to disruptions of cognitive functioning across a number of behavioral tasks including the water maze. In contrast, selective lesions to the basal forebrain cholinergic neurons using the immunotoxin, 192 IgG-saporin, which kills neurons expressing p75 nerve growth factor receptors, does not have much effect on water maze performance in mature rats and has only moderate impairing effects in aged rats [125]. Pharmacological reversal of such lesions has been challenging. For example, the nicotinic agonist, ABT-418, failed to improve measures of sustained attention in a rat-operant task in 192 IgG-saporin-lesioned rats, whereas it readily improved performance in sham-operated rats [126].
Update on novel antipsychotics and pharmacological strategies for treatment-resistant schizophrenia
Published in Expert Opinion on Pharmacotherapy, 2022
Andrea de Bartolomeis, Mariateresa Ciccarelli, Licia Vellucci, Michele Fornaro, Felice Iasevoli, Annarita Barone
Further pharmacological interventions, such as those targeting the cholinergic system, are currently being tested on the cognitive symptoms of schizophrenia [104–106]. It has been proposed that nicotinic agonists act mainly on cognitive symptoms [107], whereas muscarinic agonists appear to act on positive symptoms [108]. Although several agents targeting these receptors are currently in various stages of study, α-7 nicotinic and M1 muscarinic agonists, as well as positive allosteric modulators, are the most interesting [104,106]. For instance, the α-7 receptor agonist encenicline was tested on several measures of cognition in phase II double-blind RCT, demonstrating clinically significant improvements in schizophrenia and schizoaffective patients stabilized on concomitant atypical antipsychotics [106]. These results led to large phase III studies, which, however, showed only limited beneficial effects of this compound on cognitive deficits associated with schizophrenia [109]. With regard to muscarinic agonists, the successful combination of xanomeline + trospium is discussed in more detail below.
(E)-3-furan-2-yl-N-phenylacrylamide (PAM-4) decreases nociception and emotional manifestations of neuropathic pain in mice by α7 nicotinic acetylcholine receptor potentiation
Published in Neurological Research, 2021
Deniz Bagdas, Gulce Sevdar, Zulfiye Gul, Rabha Younis, Sinan Cavun, Han-Shen Tae, Marcelo O. Ortells, Hugo R. Arias, Mine Sibel Gurun
Further, epidemiological and clinical studies show that there is an interaction between chronic pain and tobacco use as seen in increased prevalence of tobacco use among chronic pain patients [6–10]. The reason behind being pain as a potent motivator of tobacco use can be explained in two ways: either nicotine, main ingredient in tobacco, can reduce pain or pain-related affective signs, such as depression and anxiety, increase nicotine use motivation [10–13]. A recent paper revealed that there is a correlation between nicotine dependence and the sensitivity and severity of anxiety status induced by chronic pain [13]. Indeed, previous preclinical studies show that nicotine is able to reduce both sensorial [14,15] and affective signs [15] of pain. Therefore, nicotine is a promising agent, acting as a prototypical nicotinic agonist. These dual effects of nicotine open new windows of opportunity in the use of nicotinic analogs with less side effects for pain management.
State-of-the-art behavioral and pharmacological treatments for alcohol use disorder
Published in The American Journal of Drug and Alcohol Abuse, 2019
Lara A. Ray, Spencer Bujarski, Erica Grodin, Emily Hartwell, ReJoyce Green, Alexandra Venegas, Aaron C. Lim, Artha Gillis, Karen Miotto
Varenicline is a partial α4β2 nicotinic agonist and full α7 agonist that is currently FDA approved for the treatment of nicotine dependence. Varenicline was examined as part of the NCIG initiative (127) and found to significantly reduce weekly percent heavy drinking days, drinks per day, drinks per drinking day, as well as alcohol craving. Varenicline was also well tolerated suggesting that it may serve as a promising option for AUD treatment. Moderator analyses indicated that varenicline was more efficacious in reducing drinking in smokers who also reduced their cigarette smoking (128). Recent studies investigating varencline’s efficacy in heavy drinking smokers have supported this finding (129,130). New findings indicate that varenicline’s may be more effective as an AUD treatment in men, as varenicline combined with medication management decreased heavy drinking only in men but improved smoking abstinence in both men and women (131). This medication may be especially relevant to smokers, given epidemiological estimates that 20–25% of current smokers are heavy drinkers (132).