Skeletal Muscle Relaxant Effects Research Articles

A Comparative Study of Skeletal Muscle Relaxant Effects of Thiocolchicoside, Diazepam and Their Combination in Wistar Rats Using the Rotarod Apparatus.

Introduction Thiocolchicoside (THC) is a semi-synthetic derivative of colchicoside and anaturally occurring compound in the seeds of the Gloriosa Superba L.plant. At present, it is used as a skeletal muscle relaxant. It is used to treat rheumatic arthritis, orthopaedic conditions, and trauma. Topically, it is used to relieve excruciating spasms in the muscles.It is also used to treat a wide range of conditions, which include surgical pain, cervicobrachial neuralgia, acute to chronic torticollis, Parkinson's disease, drug-induced Parkinsonism,spastic hemiplegia, tooth soreness,acute lower back pain, etc. THC is used in conjunction with non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and analgesics.By downregulating and inhibiting the synthesis of NF-κB-regulated gene products, it possesses anti-inflammatory properties. To prevent aneuploidy, the European Medical Agency has placed restrictions on the use of THC, stating that it should not be injected for five days or taken orally for longer than seven days. This is because its metabolism in the body may lead to the production of the metabolite M2. When used during pregnancy, the growing fetus is more negatively impacted. It has also been connected to infertility in men. Aim To study the skeletal muscle relaxant effects of THCin Wistar rats in comparison with standard drugs. Materials and methods The skeletal muscle relaxant activity level was measured using the rotarod apparatus. There were five groups of Wistar rats (n = 6). Group I received 0.9% normal saline (NS) as a control. Group II (test group) received THC 2 mg/kgintraperitoneally (ip).Group III (test group) received THC 4 mg/kg (ip). Group IV diazepam (DIZ) 3 mg/kg (ip) which is the standard treatment group.Group V received a combination of THC 2 mg/kg and DIZ 3 mg/kg. After treatment, retention time was noted at intervals of 30, 60, and 120 minutes. Results Group I (control), Group II (THC 2 mg/kg) and Group III (THC 4 mg/kg) did not demonstrate any skeletal muscle relaxant activity. Group IV (DIZ 3 mg/kg) and Group V (THC 2 mg/kg + DIZ 3 mg/kg) showed statistically significant skeletal muscle relaxant activity when compared to control. However, there was no statistically significant difference between the skeletal muscle relaxant activity of these two groups. This indicates that the addition of THC did not potentiate the skeletal muscle relaxant activity of DIZ. Conclusion THC didn't show skeletal muscle relaxant properties in both doses and did not potentiate the activity of DIZ.

Potential benefits of gallic acid as skeletal muscle relaxant in animal experimental models.

Background and ObjectiveMany natural bioactive chemicals have been shown to have functional activity, suggesting that they could be useful in the treatment and management of a wide range of chronic conditions. Flavonoids, which include gallic acid (GA), are the most abundant polyphenols found in nature. Skeletal muscle relaxants are drugs that reduce undesired spasms while maintaining awareness and reflexes unaffected. The purpose of this investigation was to determine if GA has any skeletal muscle relaxant properties in experimental animal models.Materials and MethodsThe muscle relaxant activity of three dosages of GA (5, 10, and 20 mg/kg) was compared to that of normal diazepam (5 mg/kg) utilizing climbing, chimney, and modified Kondziela's inverted tests. An analysis of variance (ANOVA) and a post-ANOVA Tukey multiple comparisons test were used to assess the data.ResultsAnimals given 10 and 20 mg/kg of GA had a great deal of trouble climbing up the chain, presumably because their muscles were relaxed. Similarly, rats given a high dose of GA (20 mg/kg) had a significantly (P < 0.05) longer response time in the chimney test, indicating a lack of attention and slowed muscle tone, resulting in problems with motor coordination. In inverted testing, animals given a high dose of GA had a significantly (P < 0.01) reduced holding capacity on the mesh for a longer period of time. A decrease in holding time is caused by a decrease in muscular contraction. The low dose of GA, on the other hand, failed to show muscle relaxant effect in any of the three models.ConclusionsAs a conclusion, our data show that GA has a dose-dependent skeletal muscle relaxant effect when administered orally to mice.

Anti-depressant, Anxiolytic, and the Muscle Relaxant Activity of Hydroalcoholic Extract of Cissampelos pareira Linn. Leaves.

The ethnopharmacological relevance suggests that the ethnic minorities of India use leaves of Cissampelos pareira L. as a traditional medicine for curing various psychopharmacological disorders. To evaluate anti-depressant, anxiolytic, and muscle relaxant activity of hydro-alcoholic extract of Cissampelos pareira. Leaves of Cissampelos pareira were extracted using a hydro-alcoholic solvent. The safety of hydro-alcoholic extract of Cissampelos pareira was assessed by acute oral toxicity (OECD 423). The anti-depressant activity was measured using open field test, locomotor test, despair swim test, tail suspension test. The anxiolytic activity was assessed using elevated plus maze and hole board test, and skeletal muscle relaxant activity was assessed using rotarod, grip strength, chimney, and inclined plane test. No moribund status or mortality was observed in experimental mice up to 2000 mg/kg dose of Cissampelos pareira hydro-alcoholic extract (CPHE). In the open field and actophotometer tests, CPHE 200 and 400 mg/kg treated mice significantly abridged ambulation, number of central squares crossed, total locomotion, and depicted less coordinated movements, and in despair swim and tail suspension tests, CPHE 400 mg/kg treated mice significantly decreased duration of immobility and increased number of climbing, confirming its anti-depressant effect. In an elevated plus-maze test, CPHE 200 and 400 mg/kg increased the open arm exploration, while in the hole board test, CPHE 400 mg/kg treated rats augmented the number of head dips, depicting its anxiolytic effect. In rotarod, grip strength, and inclined plane test, CPHE 400 mg/kg treated mice decreased the fall-off time on a rotating rod, suspended wire, or inclined plane. Furthermore, in the chimney test, treatment with CPHE 400 depicted less coordinated movements in mice; the mice of this group took more time to leave the cylinder, depicting its skeletal muscle relaxant effect. Based on the results, of this study, it can be concluded that CPHE 400 mg/kg exhibits strong anti-depressant, anxiolytic, and muscle relaxant effects, justifying its traditional uses.

Skeletal muscle relaxant effect of a standardized extract of Valeriana officinalis L. after acute administration in mice

Valeriana officinalis L. root extracts are traditionally taken for their sedative and anxiolytic properties and are also used for muscle relaxation. Relaxant effects were clearly observed on smooth muscle whereas data on effects on skeletal muscle are scarce and inconsistent. The aim of this study was to assess whether a standardized extract (SE) of V. officinalis had myorelaxant effects by decreasing skeletal muscle strength and/or neuromuscular tone in mice. Mice received an acute dose of V. officinalis SE (2 or 5 g/kg per os) or tetrazepam (10 mg/kg ip), a standard myorelaxant drug. Thirty minutes later, the maximal muscle strength was measured using a grip test, while global skeletal muscle function (endurance and neuromuscular tone) was assessed in a wire hanging test. Compared to tetrazepam, both doses of V. officinalis SE induced a pronounced decrease in skeletal muscle strength without any significant effects on endurance and neuromuscular tone. This study provides clear evidence that the extract of V. officinalis tested has a relaxant effect on skeletal muscle. By decreasing skeletal muscle strength without impacting endurance and neuromuscular tone, V. officinalis SE could induce less undesirable side effects than standard myorelaxant agents, and be particularly useful for avoiding falls in the elderly.

Recent Studies on the Neuropharmacological Effects of Salvia officinalis L.: A Promising Candidate for Alzheimer's Disease

Salvia is the largest genus of the Lamiaceae family including about 100 species. Salvia officinalis L. (SO) is one of the most appreciated herbs for richness of the essential oil content and its numerous biologically active compounds. SO has been used in herbal medicine for many centuries. In Islamic literature, it is considered as one of the greatest forms of healing medicine. The leaves of the plant have a wide range of biological activities, such as anti-bacterial, fungistatic, virustatic, anticancer, astringent, eupeptic and antihydrotic effects. Recently, this plant has been focused for its application in traditional medicine as well as to find new neurobiological properties. In this review, the up-todate information on the neurobiological effects of SO on the central nervous system will be reviewed. These include analgesic, memory enhancing, neuroprotective, anticonvulsant, anti-addictive, sedative, anxiolytic, and skeletal muscle relaxant effects. Furthermore, chemical compounds responsible for these effects and the clinical studies on this plant are presented and discussed.

Effect of methanol extract of Trigonella foenum-graecum L. seeds on anxiety, sedation and motor coordination.

Currently available anxiolytics cause numerous adverse effects and show craving and tolerance during long term treatment. Currently traditional medicines have been re-evaluated widely through work on various plant species. Numerous plants in traditional system show pharmacological activity with unlimited prospective for therapeutic use. Hence we planned to evaluate the effect of methanol extract of T. foenum-graecum L. seeds on anxiety, sedation and motor coordination in mice at different doses following 15days of oral feeding. Effect on anxiety was assessed by Hole board test and Light and Dark transition models.Phenobarbitone induced sleeping time and Rota rod test were performed to assess effect on sedation and motor coordination. In Hole board test, T. foenum-graecum L. seeds decreased the number of head dips in mice at all the three doses. In Light and Dark transition model, T. foenum-graecum L. seeds increased the period spent in the light box and the number of moves among the two compartments at 100 and 200mg/kg as compared to control animals. In phenobarbitone induced sleeping time, T. foenum-graecum L. seeds did not reveal any sedative effect. In Rota rod test, extract exhibited significant skeletal muscle relaxant effect at 200mg/kg (at 90min) as compared to the control animals. Results of our study shows significant antianxiety effects of T. foenum-graecum L. seeds and may also recommend improved adverse effect profile as compared to diazepam.

DIAZEPAM EFFECTS ON IMMUNE CELLS ACTIVELY INVOLVED DURING THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.

DIAZEPAM EFFECTS ON IMMUNE CELLS ACTIVELY INVOLVED DURING THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.

Addition of Clidinium-C to the 14-Day Proton Pump Inhibitor Based Triple Therapy for Helicobacter pylori Eradication\

Helicobacter Pylori (HP) is a Gram-negative, spiral-shaped, motile micro-organism that infects approximately half of the world population and the prevalence of asymptomatic infected patients appears to be age-related (1). The human is its reservoir and the transmission of this microorganism involves oral‑oral and fecal‑oral routes. The infection takes place usually in childhood, within one’s own family (between parents and children or between siblings) (2). Gastric infection by HP is actually considered to be the most relevant cause of chronic gastritis and peptic ulcer disease (PUD). It is also associated with an increased risk of mucosa associated lymphoid tissue (MALT) lymphoma and gastric cancer (3). Selection of the best drug regimens for effective eradication of HP infection is challenging. Some recent studies have suggested that the effectiveness, compliance and side-effects of quadruple regimen containing a gastric acid inhibitor, a bismuth compound and two antibiotics might be comparable with proton pump inhibitors (PPI) -based triple therapy when administered as first-line treatment for HP infection (4-6). However, in other studies showed superiority of quadruple therapy (7). Antibiotic resistance due to frequent and uncontrolled administration and high prevalence of antibiotic side effects are the most common causes of treatment failure. To increase eradication rate, as defined in the Maastricht IV report (8), several clinical trials have been initiated involving extended treatment duration, use of new antibiotics or the addition of probiotics or other drugs regimens (9). In the Maastricht Consensus Report, the 14-day treatment course was superior to the 7-day treatment. Because of the higher antibiotic resistance rates, in developing countries such as Iran, the 14-day treatment regimens is preferred. It has been shown that the large doses of antibiotics used in the triple therapy change the normal bowel flora. This may result in further gastrointestinal adverse events (8, 9). Clidinium bromide in combination with chlordiazepoxide (clidinium –C) is an anticholinergic drug which may help symptoms of cramping and abdominal stomach pain by decreasing gastric acid secretion and slowing the intestinal movement (10). Chlordiazepoxide component of this drug exerts anxiolytic, sedative, hypnotic, anticonvulsant and skeletal muscle relaxant effects. The drug may inhibit monosynaptic and polysynaptic reflexes by acting as an inhibitory neuronal transmitter or by blocking excitatory synaptic transmission. This drug may also directly depress motor nerve and muscle function. The aim of this study was to assess the effect of clidinium-C on HP eradication with a triple therapy including omeprazole, clarithromycin and amoxicillin (OCA) in patients with peptic ulcer disease (PUD). The secondary aim of the study was to investigate the efficacy and safety of clidinium-C in the prevention of side-effects related to HP eradication.

Comparative study of oral and trans nasal midazolam as a sedative premedication in paediatric patients

Background: Premedication in pediatric patient before induction of anaesthesia is of vital importance. Midazolam is a benzodiazepine which produces anxiolytic, amnestic, hypnotic and skeletal muscle relaxant effects. Objectives: To evaluate the safety, acceptability, level of sedation and ease of administration of midazolam by using oral and trans nasal route as a sedative premedication in paediatric patient. Materials and Methods: Sixty paediatric patients of ASA grade I or II, aged 2-10 years, undergoing elective surgery were randomly divided into two groups. Group I received oral syrup midazolam 0.5mg/kg and Group II received nasal spray midazolam 0.25mg/kg. Demographic profile, response to drug administration, level of sedation, separation from parents, venipuncture, induction and postoperative recovery scores were noted and statistically analyzed. Results: The study shows that children receiving oral midazolam has better acceptability (group I, 76.66%) than when administered through intranasal route (group II, 53.33%). Sedation score were better at 20 min. in intranasal group (3.06 versus 2.96) than oral group. Post anesthesia recovery scores were similar in both groups. Conclusion: On the basis of our study, we concluded that oral syrup midazolam has better acceptability while intranasal spray midazolam has slightly faster onset without prolonging recovery from anesthesia.

Neuropharmacological properties of Trichosanthes dioica root

AimTrichosanthes dioica Roxb. (Cucurbitaceae), commonly known as pointed gourd in English, is a dioecious climber grown widely in the Indian subcontinent. Traditionally, this plant has been used in India for several medicinal purposes. The present study aimed to evaluate certain neuropharmacological properties of the hydroalcoholic extract of T. dioica root (TDA) in experimental animal models. MethodsTDA (at 100 and 200 mg·kg−1 body weight, p.o.) was evaluated for anti-nociceptive activity by the acetic acid-induced writhing and tail flick methods. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effects were evaluated by using a rota-rod apparatus, and the sedative potentiating property by a phenobarbitone-induced sleep potentiation study. ResultsThe results of the present study revealed significant (P < 0.001) and dose dependent anti-nociceptive, locomotor depressant, muscle relaxant, and sedative potentiating effects of TDA, demonstrating its depressant action on the central nervous system (CNS). ConclusionFrom the present study, it can be concluded that T. dioica root possessed prominent anti-nociceptive, as well as depressant, action on the CNS, as manifested by these important neuropharmacological properties in mice.

Establishing a preliminary basis for the use of &lt;i&gt;Ocimum gratissimum&lt;/i&gt; in the traditional management of haemorrhoids

The ethanolic leaf extract of Ocimum gratissimum was tested for anti-inflammatory, analgesic and muscle relaxant properties following reports of its use in the traditional management of haemorrhoids. The isolated rabbit jejunum and phrenic nerve-diaphragm preparations were used to screen for smooth and skeletal muscle relaxant effects respectively. Anti-inflammatory and analgesic activities were evaluated using rat-paw oedema method and hot plate methods respectively. The results show that the crude extract (2.0 x 10-4 – 3.2 x 10-3g/ml) inhibited both the twitch responses to nerve stimulation and the rhythmic contractility of the rabbit jejunum in a graded manner. The extract (100-1000mg/kg) also dose-dependently inhibited egg white-induced increase in rat paw oedema and prolonged the reaction time of mice subjected to thermal stimuli. The study suggests a scientific basis for the use of Ocimum gratissimum in the traditional management of haemorrhoids. Keywords : Ocimum gratissimum, haemorrhoids, anti-inflammatory, analgesic

Anti-nociceptive activity of Mikania scandens flower in albino mice: involvement of CNS depressant role

Mikania scandens (L.) Willd. (Asteraceae), known as climbing hemp weed in English is a herbaceous climbing vine grown as a weed throughout the plains of the Indian subcontinent. The present study evaluated anti-nociceptive as well as central nervous system (CNS) activities of hydroalcoholic extract of flower from M. scandens (FMS) in Swiss albino mice. FMS (at 250 and 500 mg/kg body weight, i.p.) was evaluated for anti-nociceptive activity by acetic acid induced writhing and tail flick methods. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effect was evaluated by using rota-rod apparatus and sedative potentiating property by phenobarbitone-induced sleep potentiation study. The results of the present study revealed significant (p < 0.001) and dose dependent anti-nociceptive, locomotor depressant, muscle relaxant and sedative potentiating effects of FMS, demonstrating its depressant action on the murine CNS. From the present study, it can be concluded that the flower of M. scandens possessed prominent anti-nociceptive property along with marked depressant action on the CNS of mice.

Antidepressant and skeletal muscle relaxant effects of the aqueous extract of the Prosopis cineraria

The aqueous leaves extract of Prosopis cineraria (AEPC) is used traditionally for the treatment of various CNS disorder. The purpose of this study was to evaluate the extract for antidepressant and skeletal muscle relaxant activity. The antidepressant effect of the extract was evaluated using Forced swim test (FST). The immobility periods of control and treated mice were recorded. The antidepressant-like effect of tested compound was compared to that of imipramine (15 mg/kg. p.o). Muscle relaxant property was studied using rotarod apparatus and total fall off time for standard and control group was recorded. Phytochemical screening revealed the presence of saponins, flavonoids, alkaloids, glycosides, tannins and phenolic compounds. The leaf extract at doses of 200 mg/kg significantly decreased the duration of immobility time in FST. The efficacy of tested extract was found to be comparable to that of imipramine. Our results suggested that the aqueous extract of Prosopis cineraria leaves exerts antidepressant-like effect.

Neuropharmacological properties of Mikania scandens (L.) Willd. (Asteraceae)

Mikania scandens (L.) Willd. (Asteraceae), known as climbing hemp weed in English, is a herbaceous climbing vine grown as a weed throughout the plains of the Indian subcontinent. The present study evaluated some neuropharmacological properties of hydroalcoholic extract of aerial parts from M. scandens (HAMS) in experimental animal models. HAMS (at 250 and 500 mg/kg body weight, i.p.) was evaluated for central antinociceptive activity by tail flick method. Locomotor depressant activity was measured by means of an actophotometer. Skeletal muscle relaxant effect was evaluated by using rotarod apparatus and sedative potentiating property by phenobarbitone-induced sleep potentiation study. The results of the present study revealed significant (P<0.001) and dose-dependent central antinociceptive, locomotor depressant, muscle relaxant, and sedative potentiating effects of HAMS, demonstrating its depressant action on the central nervous system (CNS). From the present study, it can be concluded that the aerial parts of M. scandens possessed prominent depressant action on the CNS, as manifested by the important neuropharmacological properties in mice.

Anxiolytic activity of Nymphaea alba Linn. in mice as experimental models of anxiety.

Objective:The aim of the present work was to evaluate the anxiolytic effect of an ethanolic extract of Nymphaea alba Linn. in mice.Materials and Methods:The elevated plus maze test (EPMT), light and dark test (L and DT) and open field test (OFT) were used to assess the anxiolytic activity of the ethanolic extract of N. alba Linn. in mice. In addition, aggressive behavior and motor coordination was also assessed by foot shock induced aggression test (FSIAT) and rota rod test (RRT). Diazepam 1 mg/kg served as a standard anxiolytic drug, administered orally.Results:The ethanolic extract of N. alba (100 and 200 mg/kg, p.o.) significantly increased the percentage of time spent and number of entries in open arm in EPMT. In L and DT, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. In FSIAT, N. alba extract attenuated aggressive behavior related to anxiolytic activity, such as number of vocalization, leaps, rearing, biting/attacks and facing each other in paired mice. Furthermore, the extract produced skeletal muscle relaxant effect assessed by RRT.Conclusion:The results of the present study suggest that an ethanolic extract of N. alba may possess anxiolytic activity and provide a scientific evidence for its traditional claim.

Neurosedative and muscle-relaxant activities of ethyl acetate extract of Baphia nitida AFZEL

The sedative, anxiolytic and muscle-relaxant effects of the ethyl acetate leaf extract of Baphia nitida (BN) was investigated in intact mice, using the hole-board head-dip test for exploratory behavioural effect, elevated plus maze (EPM) and Y-maze (YM) models of anxiety; chimney, inclined screen, traction and climbing tests for muscle-relaxant effects. In each of these tests, BN (100–400 mg/kg, p.o.), diazepam (1 mg/kg, i.p.) or distilled water (10 ml/kg, p.o.) was administered, 30 or 60 min before performing the tests in mice. For exploratory behavioural test, number of head-dip within 15 min was counted. For EPM and YM tests, the cumulative time spent in open and closed arms was recorded within 5 min. In the muscle-relaxant tests, mice were subjected to modified models such as chimney, inclined screen, traction and climbing tests. BN produced a significant ( P < 0.05) dose-related decrease in exploratory behaviour in the head-dip test and prolongation of cumulative time spent in open arms of both EPM and YM. BN did not show any significant effect in the chimney and traction tests, but produced significant, dose-dependent muscle relaxation in the inclined screen and climbing tests. Furthermore, BN (200–1200 μg/ml) non-competitively shifted the curves of acetylcholine contractions of the toad Rectus abdominis muscle to the right. Oral doses of BN (0.1–20 g/kg) did not produce mortality, but the LD 50 when given intraperitoneally, was 645.65 mg/kg. Results suggest that the leaf extract of Baphia nitida has sedative, anxiolytic and skeletal muscle-relaxant effects and support its neurosedative use in traditional African medicine.

Skeletal muscle relaxant effect of Chonemorpha macrophylla in experimental animals

OBJECTIVE: To study the skeletal muscle relaxant property of Chonemorpha macrophylla (CM). MATERIALS AND METHOD: The skeletal muscle relaxant effect of the alcoholic extract of CM was studied on isolated frog rectus abdominis muscle, isolated rat phrenic nerve diaphragm muscle preparation and in intact young chicks. The parameter studied in the isolated muscle or isolated nerve muscle preparations was the extent of inhibition of acetylcholine or electrically-induced contraction of skeletal muscles. In intact chicks, the drug was administered i.v. in wing veins and the onset, duration and nature of paralysis were recorded. In all the experiments, the effect of the drug was compared with that of gallamine and succinylcholine. RESULTS: The alcoholic extract of CM reduced the acetylcholine-induced contraction of isolated frog rectus abdominis and electrically stimulated contractions of rat phrenic nerve diaphragm in a dose-dependent manner. In unanaesthetized chicks, it produced spastic type of paralysis with extension of the neck and limbs. The effects were similar to the effects of succinylcholine but different from those of gallamine. CONCLUSION: The alcoholic extract of CM possesses skeletal muscle relaxant property. It produces depolarizing type of muscle paralysis similar to that produced by succinylcholine.

TLC method for quantitation of methylenedioxyphenylacetone and its derivative formed in a resin-added bioreduction process

A novel class of orally active 2,3-benzodiazepines has recently been discovered and patented by Hungarian researchers [1]. Biological activity studies led to the discovery of (8R)-7-acetyl5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5h]-[2,3]benzodiazepine (Talampanel; structure I in Figure 1) a new drug, under investigation, with antiepileptic, neuroprotectant and skeletal muscle relaxant effects, as described in a review by F. Andrasi [2].

SL651498, a GABAA receptor agonist with subtype-selective efficacy, as a potential treatment for generalized anxiety disorder and muscle spasms.

SL651498 (6-fluoro-9-methyl-2-phenyl-4-(pyrrolidin-1-yl-carbonyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-1-one) was identified as a drug development candidate from a research program designed to discover subtype-selective GABA(A) receptor agonists for the treatment of generalized anxiety disorder and muscle spasms. The drug displays high affinity for rat native GABA(A) receptors containing alpha(1) (K(i) = 6.8 nM) and alpha(2) (K(i) = 12.3 nM) subunits, and weaker affinity for alpha5-containing GABA(A) receptors (K(i) = 117 nM). Studies on recombinant rat GABA(A) receptors confirm these findings and indicate intermediate affinity for the alpha(3)beta(2)gamma(2) subtype. SL651498 behaves as a full agonist at recombinant rat GABA(A) receptors containing alpha(2) and alpha(3) subunits, and as a partial agonist at recombinant GABA(A) receptors expressing alpha(1) and alpha(5) subunits. SL651498 produced anxiolytic-like and skeletal muscle relaxant effects qualitatively similar to those of benzodiazepines (BZs) [minimal effective dose (MED): 1 to 10 mg/kg, i.p. and 3 to 10 mg/kg, p.o.]. However, unlike these latter drugs, SL651498 induced muscle weakness, ataxia or sedation at doses much higher than those having anxiolytic-like activity (MED: 30 to 100 mg/kg, i.p. or p.o.). Moreover, in contrast to BZs, SL651498 did not produce tolerance to its anticonvulsant activity or physical dependence. It was much less active than BZs in potentiating the depressant effects of ethanol or impairing cognitive processes in rodents. The differential profile of SL651498 as compared to BZs may be related to its selective efficacy at the alpha(2)- and alpha(3)-containing GABA(A) receptors. This suggests that selectively targeting GABA(A) receptor subtypes can lead to drugs with increased clinical specificity. SL651498 represents a promising alternative to agents currently used for the treatment of anxiety disorders and muscle spasms without the major side effects seen with classical BZs.

A review of diazepam and its use in the horse

The application of diazepam in clinical equine practice has come into favor in recent years. This review covers the relevant studies concerning the pharmacological properties, pharmacodynamics and pharmacokinetics of diazepam and its clinical use in the horse. As a benzodiazepinic drug diazepam potentates GABA-mediated inhibition in the CNS. It exerts its principal action in the brain stem reticular formation and produces hypnotic, sedative, anxiolytic, anticonvulsant and skeletal muscle-relaxant effects. However, Diazepam is largely used in equine practice in combination with ketamine and xylazine hydrochloride for induction of anesthesia and alone as a sedative/ataractic/neuroleptic. We aimed to present a general discussion of the relevant data from pharmacokinetic, pharmacodynamic and clinical studies and subsequently to evaluate their results. The discussion is based on our results, reported partially in previous publications including an evaluation of the literature. Available knowledge concerning the pharmacology of diazepam and its application in the horse is presented. The relative merits and demerits of a variety of agents intended for use in horses are discussed, with the aim of providing practitioners and clinicians with a wider selection of safe drugs for equine sedation and premedication.