Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice

Futuro-Neto, H. A.; Costa, Patrícia Gomes; Amorim, Simone; Saraiva, Fábio Petersen; Ribeiro, Carlos Magno Rocha; Pires, JoséG.P.

doi:10.1016/s0278-5846(98)00102-x

Cited by 4 publications

(5 citation statements)

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“…Considering women have higher CYP3A4 content in the liver [ 2 ], it may be possible that nimodipine is metabolized faster in women resulting in lower drug levels and reduced efficacy. Accordingly, Futuro-Neto et al showed that female albino mice needed higher doses of nimodipine for neuroleptic-induced catalepsy than males [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial

et al. 2020

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A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1–4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1–3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1–4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine’s efficacy.

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Section: Discussionmentioning

confidence: 99%

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial

et al. 2020

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“…It has been reported that cholinergic, serotonergic, histaminergic, angiotensinergic, and glutamergic systems have effects on neuroleptic catalepsy by affecting dopaminergic transmission. In addition, a large volume of evidence has pointed out that neuronal voltage-sensitive calcium channels are involved in the modulation of dopaminergic transmission in both animals and humans (21). It has been found that nimodipine enhanced (5) and potentiated (21) haloperidol-induced catalepsy and this is thought to be related to the effects of dihydropyridine calcium channel blockers on dopamine neurotransmission (5).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a large volume of evidence has pointed out that neuronal voltage-sensitive calcium channels are involved in the modulation of dopaminergic transmission in both animals and humans (21). It has been found that nimodipine enhanced (5) and potentiated (21) haloperidol-induced catalepsy and this is thought to be related to the effects of dihydropyridine calcium channel blockers on dopamine neurotransmission (5). These results are not consistent with the results of our study in which we found that nimodipine had no effect on haloperidol-induced catalepsy.…”

Section: Discussionmentioning

confidence: 99%

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Modulation of the Antipsychotic Effect of Ziprasidone with Nimodipine

Kaygisiz

Özdemir

Baydemır

2011

Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychophar

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Modulation of the antipsychotic effect of ziprasidone with nimodipine Objective: The aim of this study was to examine the effects of chronic administration of ziprasidone, an atypical antipsychotic drug, on experimental models of psychosis and the role of nimodipine, a dihydropyridine calcium channel blocker, on these effects in mice. Methods: Experimental models of psychosis were studied in mice. Amphetamine-induced hyperlocomotion, haloperidolinduced catalepsy, and apomorphine-induced climbing tests were used as experimental models of psychosis. One and 10mg/kg doses of ziprasidone were given to mice i.p. for 10 days. Nimodipine was given as a single injection at a dose of 0.5mg/kg i.p. on the day of the experiment. Nimodipine 0.5mg/kg was also combined with the 10mg/kg dose of ziprasidone. Mice in control groups were also given saline i.p. for 10 days. A one-way ANOVA test was used as the statistical method to assess the results of the locomotor activity test and the Tukey multiple comparison test was used to compare groups. Outcomes of the climbing and catalepsy tests were analysed using the one-way ANOVA. Results: Ten mg/kg but not 1mg/kg ziprasidone significantly decreased amphetamine-induced hyperlocomotion compared to the amphetamine group. One mg/kg but not 10mg/kg ziprasidone significantly alleviated catalepsy time compared to the haloperidol group. Both doses of ziprasidone significantly reduced climbing time compared to all other groups. Nimodipine had no significant effect on amphetamine-induced hyperlocomotion, climbing and catalepsy time compared to controls, however when combined with ziprasidone, a significant increases in locomotor activity and climbing time, but no significant difference in catalepsy time were observed compared to 10mg/kg ziprasidone. Conclusion: Nimodipine when combined with ziprasidone, reversed the effect of ziprasidone on locomotor activity and climbing time but didn't change its effect on catalepsy time. We suggest that calcium channels might mediate antidopaminergic pathways and thereby the antipsychotic effect of ziprasidone, but that there is no involvement of calcium-dependent mechanisms in the cataleptogenic effect of ziprasidone.

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“…Our analysis identified a number of sex-differential drug responses that were supported by existing literature. For example, flunarizine, another CYP1A2 substrate, which is used in treating epilepsy 48 , was reported to not affect catalepsy in male mice, but attenuated catalepsy in females at the same doses 49 . Another study found that male rats formed two oxidative metabolites of flunarizine at higher rate than female rats 50 .…”

Section: Sex Differences In Dmet Gene Expression Are Linked To Sex Di...mentioning

confidence: 99%

Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes

et al. 2023

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Sex differences have been widely observed in human health. However, little is known about the underlying mechanism behind these observed sex differences. We hypothesize that sex-differentiated genetic effects are contributors of these phenotypic differences. Focusing on a collection of drug metabolism enzymes and transporters (DMET) genes, we discover sex-differentiated genetic regulatory mechanisms between these genes and human complex traits. Here, we show that sex-differentiated genetic effects were present at genome-level and at DMET gene regions for many human complex traits. These sex-differentiated regulatory mechanisms are reflected in the levels of gene expression and endogenous serum biomarkers. Through Mendelian Randomization analysis, we identify putative sex-differentiated causal effects in each sex separately. Furthermore, we identify and validate sex differential gene expression of a subset of DMET genes in human liver samples. We observe higher protein abundance and enzyme activity of CYP1A2 in male-derived liver microsomes, which leads to higher level of an active metabolite formation of clozapine, a commonly prescribed antipsychotic drug. Taken together, our results demonstrate the presence of sex-differentiated genetic effects on DMET gene regulation, which manifest in various phenotypic traits including disease risks and drug responses.

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Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice

Cited by 4 publications

References 46 publications

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial

Modulation of the Antipsychotic Effect of Ziprasidone with Nimodipine

Deciphering genetic causes for sex differences in human health through drug metabolism and transporter genes

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