Ondansetron in Multiple Sclerosis

Abstract

Two young women with chronic nausea and vertigo caused by multiple sclerosis responded to the introduction and maintenance of the 5HT3 receptor antagonist, ondansetron. Palliative care is a neglected aspect of management of degenerative neurological diseases and these cases highlight the approaches that may be used to manage difficult symptoms in the population with multiple sclerosis.

Cell Surface Expression of 5-Hydroxytryptamine Type 3 Receptors Is Controlled by an Endoplasmic Reticulum Retention Signal

“…Indeed, a COPI-independent route between the Golgi and the ER also exists (40). In support of a masking interaction involving the TMI-II region of 5-HT 3 Rs, constructs expressing this domain are capable of interacting with wild-type 5-HT 3A and 5-HT 3B subunits when co-expressed within COS-7 cells. That the mutation of this ER retention signal in 5-HT 3B to the homologous region of 5-HT 3A does not prevent ER retention implies the existence of multiple ER retention signals.…”

“…4B, right gel). The identity of the 78 kDa band is most likely BiP, because it has been identified previously to interact with 5-HT 3 and GABA A receptors (9, 21). The identity (and significance) of the other co-purifying proteins is unknown.…”

“…Cross-linking experiments were performed by the treatment of cells with dimethyl pimelimidate, 7.6 mg/ml) followed by quenching in 100 mM Tris (pH 8) prior to cell lysis. 3 Rs-The subcellular distribution and assembly of 5-HT 3 Rs was examined by heterologous expression of 5-HT 3A and 5-HT 3B subunit cDNAs in COS-7 cells. To facilitate biochemical and morphological analyses, 5-HT 3 R subunits were tagged using the Myc or hemagglutinin (HA) epitopes.…”

Cell Surface Expression of 5-Hydroxytryptamine Type 3 Receptors Is Controlled by an Endoplasmic Reticulum Retention Signal

“…Indeed, a COPI-independent route between the Golgi and the ER also exists (40). In support of a masking interaction involving the TMI-II region of 5-HT 3 Rs, constructs expressing this domain are capable of interacting with wild-type 5-HT 3A and 5-HT 3B subunits when co-expressed within COS-7 cells. That the mutation of this ER retention signal in 5-HT 3B to the homologous region of 5-HT 3A does not prevent ER retention implies the existence of multiple ER retention signals.…”

“…4B, right gel). The identity of the 78 kDa band is most likely BiP, because it has been identified previously to interact with 5-HT 3 and GABA A receptors (9, 21). The identity (and significance) of the other co-purifying proteins is unknown.…”

“…Cross-linking experiments were performed by the treatment of cells with dimethyl pimelimidate, 7.6 mg/ml) followed by quenching in 100 mM Tris (pH 8) prior to cell lysis. 3 Rs-The subcellular distribution and assembly of 5-HT 3 Rs was examined by heterologous expression of 5-HT 3A and 5-HT 3B subunit cDNAs in COS-7 cells. To facilitate biochemical and morphological analyses, 5-HT 3 R subunits were tagged using the Myc or hemagglutinin (HA) epitopes.…”

Case Report: Ketamine for Pain and Depression in Advanced Cancer

“…The role for psychostimulants, such as methylphenidate, in treating depression in patients with advanced cancer has been previously described. 31,32 Although rapidly effective for improvement of depression, often within days, methylphenidate does not provide any augmentation of pain relief, a frequent concomitant symptom in end-stage cancer.…”

Nausea and vomiting in palliative care

“…Evidence from case reports supports 5-HT 3 antagonists as effective agents in refractory nausea and vomiting in advanced cancer, 27 29 AIDS, 29 and advanced multiple sclerosis. 28 Palonosetron is a new long acting 5-HT 3 antagonist (a single dose effective for up to five days) that is less constipating than conventional 5-HT 3 antagonists. Granisetron, now available as a transdermal preparation, may offer a useful alternative to continuous subcutaneous infusions of antiemetics for patients in the community.…”

Cell Surface Expression of 5-Hydroxytryptamine Type 3 Receptors Is Controlled by an Endoplasmic Reticulum Retention Signal

“…Indeed, a COPI-independent route between the Golgi and the ER also exists (40). In support of a masking interaction involving the TMI-II region of 5-HT 3 Rs, constructs expressing this domain are capable of interacting with wild-type 5-HT 3A and 5-HT 3B subunits when co-expressed within COS-7 cells. That the mutation of this ER retention signal in 5-HT 3B to the homologous region of 5-HT 3A does not prevent ER retention implies the existence of multiple ER retention signals.…”

“…4B, right gel). The identity of the 78 kDa band is most likely BiP, because it has been identified previously to interact with 5-HT 3 and GABA A receptors (9, 21). The identity (and significance) of the other co-purifying proteins is unknown.…”

“…Cross-linking experiments were performed by the treatment of cells with dimethyl pimelimidate, 7.6 mg/ml) followed by quenching in 100 mM Tris (pH 8) prior to cell lysis. 3 Rs-The subcellular distribution and assembly of 5-HT 3 Rs was examined by heterologous expression of 5-HT 3A and 5-HT 3B subunit cDNAs in COS-7 cells. To facilitate biochemical and morphological analyses, 5-HT 3 R subunits were tagged using the Myc or hemagglutinin (HA) epitopes.…”

Case Report: Ketamine for Pain and Depression in Advanced Cancer

“…The role for psychostimulants, such as methylphenidate, in treating depression in patients with advanced cancer has been previously described. 31,32 Although rapidly effective for improvement of depression, often within days, methylphenidate does not provide any augmentation of pain relief, a frequent concomitant symptom in end-stage cancer.…”

Nausea and vomiting in palliative care

“…Evidence from case reports supports 5-HT 3 antagonists as effective agents in refractory nausea and vomiting in advanced cancer, 27 29 AIDS, 29 and advanced multiple sclerosis. 28 Palonosetron is a new long acting 5-HT 3 antagonist (a single dose effective for up to five days) that is less constipating than conventional 5-HT 3 antagonists. Granisetron, now available as a transdermal preparation, may offer a useful alternative to continuous subcutaneous infusions of antiemetics for patients in the community.…”

Cell Surface Expression of 5-Hydroxytryptamine Type 3 Receptors Is Controlled by an Endoplasmic Reticulum Retention Signal

“…Indeed, a COPI-independent route between the Golgi and the ER also exists (40). In support of a masking interaction involving the TMI-II region of 5-HT 3 Rs, constructs expressing this domain are capable of interacting with wild-type 5-HT 3A and 5-HT 3B subunits when co-expressed within COS-7 cells. That the mutation of this ER retention signal in 5-HT 3B to the homologous region of 5-HT 3A does not prevent ER retention implies the existence of multiple ER retention signals.…”

“…4B, right gel). The identity of the 78 kDa band is most likely BiP, because it has been identified previously to interact with 5-HT 3 and GABA A receptors (9, 21). The identity (and significance) of the other co-purifying proteins is unknown.…”

“…Cross-linking experiments were performed by the treatment of cells with dimethyl pimelimidate, 7.6 mg/ml) followed by quenching in 100 mM Tris (pH 8) prior to cell lysis. 3 Rs-The subcellular distribution and assembly of 5-HT 3 Rs was examined by heterologous expression of 5-HT 3A and 5-HT 3B subunit cDNAs in COS-7 cells. To facilitate biochemical and morphological analyses, 5-HT 3 R subunits were tagged using the Myc or hemagglutinin (HA) epitopes.…”

Case Report: Ketamine for Pain and Depression in Advanced Cancer

“…The role for psychostimulants, such as methylphenidate, in treating depression in patients with advanced cancer has been previously described. 31,32 Although rapidly effective for improvement of depression, often within days, methylphenidate does not provide any augmentation of pain relief, a frequent concomitant symptom in end-stage cancer.…”

Nausea and vomiting in palliative care

“…Evidence from case reports supports 5-HT 3 antagonists as effective agents in refractory nausea and vomiting in advanced cancer, 27 29 AIDS, 29 and advanced multiple sclerosis. 28 Palonosetron is a new long acting 5-HT 3 antagonist (a single dose effective for up to five days) that is less constipating than conventional 5-HT 3 antagonists. Granisetron, now available as a transdermal preparation, may offer a useful alternative to continuous subcutaneous infusions of antiemetics for patients in the community.…”