Tizanidine

Tizanidine is an α2-adrenergic receptor agonist and inhibits neurotransmitter release from CNS noradrenergic neurons.

Low doses of tizanidine synergize the anti-nociceptive and anti-inflammatory effects of ketorolac or naproxen while reducing of side effects.[Pubmed:28315341]

Eur J Pharmacol. 2017 Jun 15;805:51-57.

The aim of the present study was to determine whether Tizanidine, an alpha2-adrenoceptor agonist, is able to increase the anti-inflammatory and anti-nociceptive effects of naproxen and ketorolac with a low incidence of gastric injury and spontaneous activity in rats. The anti-inflammatory effect was assayed in a carrageenan test, and oral administration of Tizanidine (ED40 =0.94+/-0.2mg/kg), naproxen (ED40=3.18+/-0.4mg/kg), and ketorolac (ED40=16.4+/-1.9mg/kg) showed a dose-dependent effect on inflammation. The anti-nociceptive effect was assayed in the formalin test, and administration of Tizanidine (ED40=0.39+/-0.06mg/kg, p.o.), naproxen (ED40=33.9+/-3.9mg/kg, p.o.) or ketorolac (ED40=6.49+/-1mg/kg, p.o.) each showed a dose-dependent anti-nociceptive effect. The effects of combinations of Tizanidine/naproxen and Tizanidine/ketorolac were determined considering their ED40 at a rate of 1:1. Additionally, the Tizanidine/naproxen and Tizanidine/ketorolac combinations showed anti-inflammatory and anti-nociceptive effects. The Tizanidine/ketorolac combination was more potent than Tizanidine/naproxen, in both inflammatory (interaction index=0.03 Tizanidine/ketorolac and 0.07 Tizanidine/naproxen) and nociceptive (interaction index=0.005 Tizanidine/ketorolac and 0.01 Tizanidine/naproxen) processes. In both cases, Tizanidine improved naproxen and ketorolac gastrointestinal tolerability by 50%. Furthermore, co-administration of Tizanidine with naproxen or ketorolac did not modify the spontaneous activity in the same way as individual Tizanidine administration. Considering that Tizanidine increases the anti-inflammatory and anti-nociceptive effects of naproxen or ketorolac, with an increase in gastric tolerability, Tizanidine could provide therapeutic advantages in the clinical treatment of inflammation and pain.

Nanotransfersomes-loaded thermosensitive in situ gel as a rectal delivery system of tizanidine HCl: preparation, in vitro and in vivo performance.[Pubmed:28156169]

Drug Deliv. 2017 Nov;24(1):252-260.

The purpose of the current study was to develop Tizanidine HCl (TIZ; a myotonolytic agent used for treatment of spasticity) loaded nanotransfersomes intended for rectal administration, aiming to bypass the hepatic first-pass metabolism. TIZ-loaded nanotransfersomes were prepared by thin-film hydration method followed by characterization for various parameters including entrapment efficiency, vesicle diameter, in vitro release and ex vivo permeation studies. Transfersomal formulation composed of phosphatidylcholine and Tween 80 at a weight ratio of (85:15) gave a satisfactory results. It exhibited encapsulation efficiency of 52.39%, mean diameter of 150.33 nm, controlled drug release over 8 h and good permeation characteristics. Optimum formula was then incorporated into Pluronic-based thermoreversible gel using hydroxypropyl methylcellulose (HPMC) as a mucoadhesive polymer. Pharmacokinetic study was performed by rectal administration of transfersomes-loaded in situ gel to rabbits and compared with oral drug solution and rectal TIZ in situ gel. The pharmacokinetic study revealed that the transfersomal formulation successively enhanced the bioavailability of TIZ by about 2.18-fold and increased t1/2 to about 10 h as compared to oral solution. It can be concluded that encapsulation of TIZ into nanotransfersomes can achieve a dual purpose of prolonged TIZ release and enhanced bioavailability and so may be considered as a promising drug delivery system for the treatment of spasticity.