# The impact of tizanidine, thiocolchicoside, and cyclobenzaprine on vascular function in ovariectomized rats

## TL;DR

This study examines how three muscle relaxants affect blood vessel function in rats that model menopause, finding that some drugs worsen vascular health.

## Contribution

The study evaluates the vascular effects of tizanidine, thiocolchicoside, and cyclobenzaprine in an ovariectomized rat model of menopause.

## Key findings

- Tizanidine and cyclobenzaprine reduced body weight gain and improved receptor-dependent contractile sensitivity in ovariectomized rats.
- Tizanidine had calcium antagonistic effects but worsened endothelial function in the model.
- High-dose or prolonged use of thiocolchicoside and cyclobenzaprine may negatively affect vascular reactivity.

## Abstract

Menopause is associated with increased vascular risk. This study investigated the effects of 3 centrally acting muscle relaxants—tizanidine (TZ), thiocolchicoside (TCC), and cyclobenzaprine (CBZ)—on vascular reactivity in ovariectomized (OVX) rats as a model of menopause.

Body weight, blood glucose, blood pressure, and heart rate were recorded, and the rats underwent oophorectomy surgery. Eight weeks after the operation, the rats were divided into 5 groups: sham operated rats, OVX rats, OVX rats treated with TZ (OVX + TZ), OVX rats treated with TCC (OVX + TCC), and OVX rats treated with CBZ (OVX + CBZ). All drug treatments were at a dosage of 2 mg/kg/day for 2 weeks. Isolated rat aortas were suspended in a tissue chamber. Vascular reactivity was assessed using increasing concentrations of phenylephrine, acetylcholine, and sodium nitroprusside, as well as potassium chloride at a concentration of 40 mM.

Body weight, phenylephrine sensitivity, and potassium chloride responses significantly increased with OVX. TZ and CBZ decreased body weight gain and ameliorated receptor-dependent contractile sensitivity. TZ and CBZ had calcium antagonistic effects on vascular smooth muscle. TZ deteriorated endothelial function.

TZ cannot be considered a safe medication for patients with endothelial dysfunction. In high doses and for longer periods, TCC and CBZ might also have deleterious effects on vascular reactivity. These findings are noteworthy from the perspective of rational drug therapy.