Disease relevance of Ternelin

• Tizanidine treatment of spasticity caused by multiple sclerosis: results of a double-blind, placebo-controlled trial. US Tizanidine Study Group [1].
• The most common adverse events during tizanidine treatment were somnolence, xerostomia, and fatigue [2].
• Tizanidine produced a significantly greater reduction than placebo in spasms and clonus (patient diaries) but no significant differences in Ashworth scores [1].
• Because tizanidine reinforces presynaptic as well as Ib nonreciprocal inhibition, it may reduce both brisk tendon jerks and muscle hypertonia [3].
• While drowsiness is a frequently reported adverse effect with both agents, subjective muscle weakness appears to be less of a problem with tizanidine than with baclofen [4].

Psychiatry related information on Ternelin

• Tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole] is able to increase the pain threshold in the tail-flick test in mice [5].
• The effects caused by tizanidine administration may be due to its alpha 2 receptor agonist activity interfering with a mechanism involved in the regulation of these previously mentioned withdrawal symptoms [6].
• ES2 produced by four times the sensory threshold was lengthened after tizanidine administration [7].
• The effect of tizanidine on maximal electroshock seizures (MES) in mice [8].
• Objectives of this study were to assess efficacy and effects on psychomotor performances of thiocolchicoside (TCC) and tizanidine (TZ) compared to placebo [9].

High impact information on Ternelin

• Drug interaction of tizanidine and ciprofloxacin: Case report [10].
• Tizanidine seems to be a useful probe drug for measuring presystemic metabolism by CYP1A2 [11].
• The mean elimination half-life of tizanidine was prolonged from 1.5 to 4.3 hours (P =.00004) by fluvoxamine [12].
• RESULTS: Ciprofloxacin increased the area under the plasma concentration-time curve from time 0 to infinity [AUC(0-infinity)] of tizanidine by 10-fold (range, 6-fold to 24-fold; P < .001) and its peak concentration by 7-fold (range, 4-fold to 21-fold; P < .001), whereas its elimination half-life was only prolonged from 1.5 to 1.8 hours (P = .007) [11].
• OBJECTIVE: Our objective was to study the effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of tizanidine, a centrally acting skeletal muscle relaxant [12].

Chemical compound and disease context of Ternelin

• RESULTS: The administration of 3.0 microg intrathecal clonidine or 5.0 microg tizanidine significantly reversed both thermal and mechanical hyperalgesia [13].
• Systemic tizanidine hydrochloride (Zanaflex) partially decreases experimental postoperative pain in rats [14].
• The time to loss of consciousness in the Tizanidine group (60.2 +/- 22.5 s) was significantly shorter than that in the Control group (73.7 +/- 26.3 s) (P = 0.03) [15].
• A double-blind study was carried out in 105 patients with chronic spasticity associated with hemiplegia in order to compare the efficacy and tolerability of tizanidine with that of diazepam [16].
• OBJECTIVE: To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril [17].

Biological context of Ternelin

• Pharmacokinetics and pharmacodynamics of tizanidine [18].
• Tizanidine: neuropharmacology and mechanism of action [19].
• Effect of intrathecal tizanidine on antinociception and blood pressure in the rat [20].
• Moxonidine and tizanidine also displayed selectivities for a high affinity component of the platelet I1 binding sites over alpha-2 adrenoceptors [21].
• Tizanidine (250-500 micrograms) did not change heart rate [22].

Anatomical context of Ternelin

• It was concluded that, overall, tizanidine is effective in reducing spasticity in patients with spinal cord injury [2].
• 6. Two hours after the ingestion of tizanidine, an alpha(2)-adrenergic receptor agonist known to selectively depress the transmission in the group II afferent pathway, the medium latency reflex was strongly depressed (P = 0.007), whereas the short latency component was unchanged (P = 0.653) [23].
• On the basis of the present results, taken together with previous observations that tizanidine transiently inactivates neurons of the nucleus locus coeruleus, it is proposed that the reflex depression may be caused by a removal of a descending noradrenergic facilitation exerted on spinal reflex transmission [24].
• This interpretation leaves open further possible actions of tizanidine exerted directly on spinal interneurons [24].
• Tizanidine but not placebo decreased the quadriceps muscle and global lower limb Ashworth scores (2.9 (0.2) to 1.9 (0.3), p<0.001; and 12 (0.7) to 9.5 (0.8), p<0.0001, respectively) [25].

Associations of Ternelin with other chemical compounds

• Both the tail-pinch potential and the ipsilateral slow VRP were depressed by application to the spinal cord of tizanidine (2-3 microM), diazepam (2 microM) and eperisone (100-200 microM) [26].
• SETTING: Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada. DESIGN: A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg) [27].
• 1. The effect of the myorelaxant drugs baclofen, diazepam and tizanidine have been compared on in vitro preparations of baby rat spinal cord and adult rat superior cervical ganglion [28].
• Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists [29].
• Selective antinociceptive effects of tizanidine (DS 103-282), a centrally acting muscle relaxant, on dorsal horn neurones in the feline spinal cord [30].

Gene context of Ternelin

• METHODS: The effect of CYP isoform inhibitors on the elimination of tizanidine was studied using pooled human liver microsomes [31].
• CONCLUSIONS: Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels [27].
• In spinalized preparations, a net facilitatory alpha 1-mediated action may be revealed by the higher doses of tizanidine that would be unopposed by the alpha 2-mediated disfacilitation [32].
• Aspirin (150 mg/kg i.v.), proacetaminophen (300 mg/kg i.v.) and tizanidine, a centrally acting myorelaxant (0.25-1 mg/kg i.v.), had no effect on the number of Fos-like immunoreactivity neurons induced by heat stimulation [33].
• RESULTS: Incubation of tizanidine (80 nm) with human liver microsomes resulted in time- and NADPH-dependent substrate consumption with a half-life of 50 min, initial reaction velocity of 1.1 pmol x min-1 x mg-1 protein and intrinsic clearance of 17 ml x min-1 x kg-1 [31].

Analytical, diagnostic and therapeutic context of Ternelin

• Summary of combined clinical analysis of controlled clinical trials with tizanidine [34].
• This multicenter study (14 sites) assessed the efficacy and safety of oral tizanidine in patients who had spinal cord injury of > 12 months' duration [2].
• Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure [20].
• Wide interpatient variability in the effective plasma concentrations of tizanidine means that the optimal dosage must be titrated over 2 to 4 weeks for each patient (dosages of 2 to 36 mg/day have been used in clinical trials) [4].
• In a double blind, placebo controlled, cross over study the correlations between single doses (2, 4, and 8 mg), plasma concentrations, and antispastic action of tizanidine were investigated in 16 patients with extensor spasticity of the legs due to multiple sclerosis [35].

References