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Serotonin Selective Reuptake Inhibitors (SSRIs) and Female Sexual Dysfunction (FSD): Hypothesis on its Association and Options of Treatment

Rappek NAM, Sidi H, Kumar J, Kamarazaman S, Das S, Masiran R, et al.

Curr Drug Targets, 2018;19(12):1352-1358.
PMID: 28025939 DOI: 10.2174/1389450117666161227142947

Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter- playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potential confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies. The exact mechanism of FSD-induced SSRIs is unknown. It has been postulated that although SSRIs may modulate other neurotransmitter system such as nitric oxide (NO), noradrenergic and dopamine in inducing FSD. In the present review, we highlight current evidence regarding potential mechanism of SSRIs in causing FSD, which include low sexual desire (low libido), arousal difficulties (lack of lubrication), and anorgasmia. The specific association of FSD to SSRI use, has not been ellucidated. The relationship is dose-dependent, and may vary among the groups with respect to mechanism of serotonin and dopamine reuptake, induction of release of prolactin from the pituitary gland, anticholinergic side-effects, inhibition of NO synthesis and emotional-memory circuit encryption for sexual experiences. Various interventional strategies exist regarding the treatment of SSRI-induced FSD and this includes tolerance, titration dosage, substitution to another antidepressant drug and psychotherapy. There is a need of better understanding of SSRIs-induced FSD for better treatment outcome.

Matched MeSH terms: Serotonin Antagonists/pharmacology; Serotonin Antagonists/therapeutic use
Zerumbone alleviates chronic constriction injury-induced allodynia and hyperalgesia through serotonin 5-HT receptors

Chia JSM, Omar Farouk AA, Mohamad AS, Sulaiman MR, Perimal EK

Biomed Pharmacother, 2016 Oct;83:1303-1310.
PMID: 27570173 DOI: 10.1016/j.biopha.2016.08.052

Zerumbone, a bioactive sesquiterpene isolated from Zingiber zerumbet (Smith), has shown to exert antiallodynic and antihyperalgesic effects in neuropathic pain mice model in our recent study. The mechanism through which zerumbone alleviates neuropathic pain has yet to be elucidated. Thus, this study aimed to determine whether the serotonergic system, part of the descending pain modulation pathway, contributes to the antineuropathic effect of zerumbone. Participation of the serotonergic system in zerumbone-induced antiallodynia and antihyperalgesia was assessed using Dynamic Plantar Aesthesiometer von Frey test and Hargreaves plantar test respectively in chronic-constriction injury mice model. Administration of ρ-chlorophenylalanine (PCPA, 100mg/kg, i.p.) for four consecutive days to deplete serotonin (5-HT) prior to zerumbone administration blocked the antiallodynic and antihyperalgesic effects of zerumbone. Further investigation with 5-HT receptor antagonists methiothepin (5-HT1/6/7 receptor antagonist, 0.1mg/kg), WAY-100635 (5-HT1A receptor antagonist, 1mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3mg/kg) and ondansetron (5-HT3 receptor antagonist, 0.5mg/kg) managed to significantly attenuate antiallodynic and antihyperalgesic effects of zerumbone (10mg/kg). These findings demonstrate that zerumbone alleviates mechanical allodynia and thermal hyperalgesia through the descending serotonergic system via 5-HT receptors 1A, 1B, 2A, 3, 6 and 7 in chronic constriction injury neuropathic pain mice.

Matched MeSH terms: Serotonin Antagonists/isolation & purification; Serotonin Antagonists/therapeutic use*
Fulltext The intraperitoneal ondansetron for postoperative pain management following laparoscopic cholecystectomy: A proof-of-concept, double-blind, placebo-controlled trial

Abdelaziz DH, Boraii S, Cheema E, Elnaem MH, Omar T, Abdelraouf A, et al.

Biomed Pharmacother, 2021 Aug;140:111725.
PMID: 34015580 DOI: 10.1016/j.biopha.2021.111725

BACKGROUND: Pain after laparoscopic cholecystectomy remains a major challenge. Ondansetron blocks sodium channels and may have local anesthetic properties.
AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy.
METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups.
RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively).
CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.

Matched MeSH terms: Serotonin Antagonists/therapeutic use*
Fulltext Involvement of monoaminergic system in the antidepressant-like effect of aqueous extract of Channa striatus in mice

Saleem AM, Taufik Hidayat M, Jais AM, Fakurazi S, Moklas MA, Sulaiman MR, et al.

Eur Rev Med Pharmacol Sci, 2013;17(15):2019-22.
PMID: 23884821

BACKGROUND: In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown.
AIM: The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice.
MATERIALS AND METHODS: AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance.
RESULTS: The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST.
CONCLUSIONS: The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.

Matched MeSH terms: Serotonin Antagonists/pharmacology