Anxiolytics and Anticonvulsants

Alprazolam

By M. Younus, BVSc, MVSc, SKUAST-K

Alprazolam (Benzodiazepine class).

  • Anti-anxiety medication for dog and cat.
  • Panicolytic.
  • Given as extra label drug.

MOA:

  • Alprazolam binds and stimulates three receptors in CNS Viz BNZ-1, BNZ-2 and GABA receptors.

Effects:

  • Sedation and anti-anxiety ( BNZ-1).
  • Effect on memory, coordination, muscle relaxation, and anticonvulsive activity( BNZ-2).
  • Inhibition of the nervous system and calming effect (GABA).

Side Effects:

  • Increased appetite.
  • uncoordinated walking.
  • Effect on Learning.
  • Paradoxical reaction (opposite effects such as aggression, anxiety, or agitation) – rare side effect .
  • Behavioral changes in cats.

Species:

  • Dog and Cat.

Indication:

  • Panic disorder due to thunder storm , firework, blasts etc.

Dose:

  • 0.25mg or 0.5mg total dose PO 1/2-1 hour before triggering event.

Contra indication:

  • Allergic to drug.
  • Paradoxical reaction.
  • Use cautiously in glaucoma ,weak and pregnant animals.
  • Pets on Ketoconazole and itraconazole (CYP3A inhibitors). Note: CYP3As mediate metabolism of Alprazolam.

Brands:

Available as human brands in india.

  • Xanax 0.5mg tab ( Pfizer India).

Composition: Each tab contains 0.5mg Alprazolam.

  • Alprax 0.25mg/0.5mg tab( Torrent India).

Composition: Each tab contains 0.25mg/0.5mg Alprazolam

  • Aaram 0.25mg/0.5mg tab( BMW India).

Composition: Each tab contains 0.25mg/0.5mg Alprazolam.

Abizox 0.25mg/0.5mg tab (Alpic Biotech India).

Composition: Each tab contains 0.25mg/0.5mg Alprazolam.

Azaperone

By M. Younus, BVSc, MVSc, SKUAST-K

Azaperone( butyrophenone neuroleptic sedative).

  • For the use in Pigs with aggressive behaviour

MOA:

  • Azaperone is a dopamine receptor blocker that causes sedation, with higher doses potentially leading to motor symptoms like catalepsy.
  • It has antiemetic effects by blocking apomorphine.
  • Additionally, it can slightly lower body temperature by inhibiting the hypothalamic heat regulation center and dilating blood vessels.
  • When given to pigs at therapeutic doses, azaperone helps improve breathing and counteracts the depressive effects of opiates.

Effects:

  • Sedative and antiaggressive effects for 6-8 hours.

Side effects:

  • Bradycardia with low heart output, dilated blood vessels, and lower blood pressure.
  • At high levels, azaperone blocks histamine and serotonin.

Species:

  • Pig.

Dose:

  • Aggressive behaviour (re-grouping, devouring of piglets), obstetrics 2 mg /kg IM.
  • Cardiovascular stress 0.4 mg /kg IM.
  • Transport stress in piglets, weaners and boars 1.0 mg /kg IM.
  • Transport stress in sows and fattening pigs 0.4 mg /kg .
  • Premedication in local and general anaesthesia, nutritional muscular dystrophy 1 – 2 mg /kg IM.
  • Use long needle to prevent deposition into fat
  • Do not administer more than 5 ml per injection site.
  • Occasional deaths in Vietnamese Pot Bellied pigs may occur due to injections into fat, which can lead to slow effects and require more doses, risking overdose. It is crucial not to exceed the recommended dose for this breed. If the pig does not respond to the first injection, allow it to recover fully before administering another dose on a different day.

Indication:

  • Aggressive behaviour (re-grouping, devouring of piglets).
  • Treatment of stress.
  • Prevention of stress.

Contraindication:

  • Avoid using in very cold conditions, as it may lead to cardiovascular collapse and hypothermia due to peripheral vasodilation.
  • It is not suitable for transporting or regrouping pigs that will be slaughtered before the withdrawal period ends.
  • Do not use in cases of hypersensitivity to the active substance or any excipients.

Brands:

  • Sresealth 50ml inj vial (Livealth Biopharma India).

Composition: Each ml contain 40mg azaperone.

Diazepam

By M. Younus, BVSc, MVSc, SKUAST-K

Diazepam ( benzodiazepine).

  • Approved for dog and cat.

MOA:

  • Diazepam binds GABA receptor in limbic system and hypothalamus thus enhance inhibitory effect of gamma aminobutyric acid( GABA). This leads to increase in opening of chloride channel and influx of chloride ions into the neurons .

Effects:

  • Hyperpolarization of membrane and decrease in neuronal excitability.

Species:

  • Cat, Dog, Small mammals, Horse ,Birds and exotic species.

Indication:

  • Anxiety.
  • Urine Spraying in Cat.
  • Muscle relaxants.
  • Pre anaesthetic sedation.
  • Lack of appetite.
  • Seizures.
  • Irretable bowel Syndrome.
  • Panic disorder.
  • Excessive grooming.

Dose:

  • 0.5 to 2 mg /kg IV/ Rectal/ intranasal/ PO Stat/OD/BD/TD as per indication in dog.
  • 0.25-1mg/kg IV Stat/OD/BD as per need in cat.
  • 0.05-0.1mg/kg in combination with Xylazine and Ketamine IV in horse.
  • 0.25-0.50 mg/kg IM, IV OD for 2-3 days in poultry.

Contra indication:

  • Allergic to drug.
  • Severe liver disease.
  • Oral use in cat causes liver disease.
  • Pregnancy particularly first trimester.
  • Use cautiously in working dogs.

Brands:

  • Rajcalm 10ml inj vial ( Hatvet India).

Composition: Each ml contains 5mg Diazepam.

Human brands in India.

  • Diazepam 2ml inj ampule( Hameln Pharmaceuticals India).

Composition: Each ml contains 5mg Diazepam.

  • Valium 10 tab ( Roche India).

Composition: Each tab contains 10mg Diazepam.

Clonazepam

By M. Younus, BVSc, MVSc, SKUAST-K

Clonazepam

  • Long-acting benzodiazepine with anticonvulsant, muscle relaxant and anxiolytic properties.
  • Hepatic enzyme inducers like phenobarbital and phenytoin, may accelerate the metabolism of clonazepam.
  • Antifungal imidazoles may increase clonazepam levels.

MOA:

  • Clonazepam binds to benzodiazepine site of the GABA-A receptor and potentiates the action of gamma-aminobutyric acid (GABA) .
  • GABA-A receptor is a ligand-gated chloride ion selective channel whose endogenous ligand is GABA (gamma-aminobutyric acid).
  • The binding causes conformational change in the GABA-A receptor’s chloride channel, leading to increased opening of chloride channels and influx of chloride ions into the neurons.
  • Clonazepam also affects glutamate decarboxylase activity.

Effects:

  • Modulation of GABA signaling calms down and reduces neuron excitability.

Side effects:

  • Mild sedation and respiratory suppression at higher doses.
  • Acute hepatic necrosis, sedation, and ataxia(potential side effects in cats).

Species :

  • Dog and Cat.

Indication:

  • Muscular hypertonicity (episodic falling) in the Cavalier King Charles Spaniel.
  • Behavior problems in both cats and dogs and hyperaesthesia in cats.
  • Epilepsy in cats.

Dose:

  • 0.1-0.5 mg/kg p.o. q8–12h in dogs.
  • 0.5 mg/animal p.o. q12–24h in cats.
  • While discontinuing the drug after long-term use, the dosage should be gradually reduced.

Contra indication:

  • CNS depression, respiratory depression, severe muscle weakness, or hepatic impairment.
  • Acute narrow-angle glaucoma.

Brands:

Human brands available in India:

  • Clonax 1mg tab(AN Pharma India).
  • Clonapik 0.5mg/1mg tab ( Aarpik Pharmaceuticals India).
  • Revotril 0.5mg/1mg tab( AHPL India).
  • Melzap-MD 0.5mg tab ( Alkem India).
  • Melzap 2mg tab ( Alkem India).
  • Petril-MD 0.5 mg tab ( Microlabs India).
  • Petri 1mg/2mg tab ( Microlabs India).

Gabapentin

By M. Younus, BVSc, MVSc, SKUAST-K

Gabapentin (Structural Analogue of GABA).

  • Anticonvulsant agent.

MOA:

  • Gabapentin binds to α2δ, an auxiliary protein connected to the main α1 subunit (the channel-forming protein) of high voltage-activated voltage-dependent calcium channels. This binding prevents the delivery of the calcium channels to the cell membrane and decreases signaling, leading to decreased neurotransmitter release.
  • Also prevents interactions of α2δ with NMDA receptors, neurexins, and thrombospondins.

Effects:

  • Stabilization of over excited neurons and relief from pain.

Side effects:

  • Sedation and loss of coordination.

Dose:

  • 10 mg/kg, PO/BD.

Species:

  • Dog ,Cat and Foal.

Indication:

  • Seizures.
  • Chronic neuropathy
  • Anxiety.
  • Chronic joint pain.

Contra Indication:

  • Hypersensitivity to drug.
  • Use cautiously during pregnancy.
  • Use two hours after antacid administration.
  • Kidney disease.

Brands:

  • Vetina Gabapentin 100 tab( Vetina India).

Composition: Each tab contains 100mg Gabapentin.

  • Gabapet 100/300 tab ( Dogue India).

Composition: Each tab contains 100mg Gabapentin.

Levetiracetam

By M. Younus, BVSc, MVSc, SKUAST-K

Levetiracetam (pyrrolidine class).

  • Also known as Keppra.
  • Extra label anti-convulsant .

MOA:

  • Levetiracetam binds to SV2A ( synaptic vesicle membrane protein) and modulates its function.
  • Also inhibits presynaptic calcium channels and neurotransmitter release is decreased under pathological conditions.

Effects:

  • Excessive neuron transmission is inhibited without affecting normal transmission.

Species:

  • Cat and Dog.

Dose:

Initial Dosage:

  • 20 mg/kg PO TID in dog.
  • 10–20 mg/kg PO TID in cat.

Incremental Dosage.

  • 20mg/ kg after every two weeks if therapeutic response is not seen or tolerance to drug.
  • Reduce dosage if adverse effects are noticed.

Indication:

  • Epilepsy/ Convulsions.
  • As adjunct to other anticonvulsants
  • Seizures refractory to other anticonvulsants e.g. phenobarbital and bromide therapy.

Contraindication:

  • Not recommended for use in pregnant or nursing pets.
  • Allergy to drug.

Brands:

Available as human brands in India.

  • Keppra 250/ 500mg tablet ( UCB India ).
  • Lenerve 250/ 500mg tablet(East West Pharma India).
  • Levepsy 250/ 500mg tablet( Cipla India).
  • Leveron 250/ 500mg tablet( Macleods India).

Flumazenil

By M. Younus, BVSc, MVSc, SKUAST-K

Flumazenil(1,4-imidazobenzodiazepine).

  • Benzodiazepine antagonist derived from the antibiotic anthramycin.

MOA:

  • Flumazenil displaces benzodiazepines from GABA receptors to reverse their depressive effects due to its higher affinity for the receptors.

Effects:

  • Reversing benzodiazepine effects.

Dose:

  • 0.01 mg/kg IV several times till toxic effects are over in dog and cat. Use IV catheter other wise leakage may cause necrosis and sloughing.

Species:

  • Dog and Cat.

Indication:

  • Benzodiazepine toxicosis in dog and cat.
  • To improve neurological signs in dog with severe hepatic encephalopathy.

Contraindication:

  • Seizures.
  • Head injury.
  • Tricyclic antidepressant toxicosis.
  • Don’t give higher dose than therapeutic dose. At higher dose Flumazenil acts Benzodiazepine receptor agonist.

Brands:

Available as Human brands.

  • Romazicon (Genentech USA) 5-mL multiple-use vial containing 0.1 mg/mL flumazenil.
  • Fludot (Neon India)5ml ampule containing 0.5mg/ml flumazenil.

Clopramine

By M. Younus, BVSc, MVSc, SKUAST-K

Clopramine (Tricyclic antidepressants).

  • Approved for behavior disorder in dogs.

MOA:

  • Clopramine inhibits serotonin re uptake and noradrenaline uptake by nerve cells in brain.
  • Clopramine also inhibits NAMDA receptors in CNS.

Effects:

  • Anti psychotic effect.
  • The level of serotonin in brain gets increased.

Side Effects:

  • GIT upset ( vomiting, diarrhea /constipation ).
  • Lack of appetite and dry mouth.
  • Raised liver enzymes.
  • Difficulty in urination.
  • Serious side effects include abnormal bleeding, fever, seizures, , irregular heart beat. and over excitement.
  • Cats are more susceptible to side effects.

Species:

  • Dog, Cat and Birds.

Indication:

  • Behavioral disorder such as separation anxiety in dog.
  • Urine spraying in cat and birds.
  • Feather picking in birds.

Dose:

  • 2-4 mg /kg PO BD in dog.
  • 0.25-0.5mg/kg PO OD in cat.
  • 0.04mg/kg /day PO BD in birds.
  • The effect is seen after 2- 3 weeks of usage of drug.

Contraindication:

  • Seizures.
  • Liver insufficiency.
  • Aggressive dogs.

Brands:

Available as Human brands:

  • Anafranil -25 tab ( Novartis India).

Composition: Each tab contains 25mg Clomipramine.

  • Biolomin 50 mg tab( Chemo Biologicals India).

Composition: Each tab contains 50mg Clomipramine

  • Clofranil 10mg/25mg/50mg tab ( Sun Pharma India).

Composition: Each tab contains 10mg /25mg/50mg Clomipramine.

  • Clofranil-SR 75 mg tab( Sun Pharma India).

Composition: Each tab contains 75mg Clomipramine.

  • Clomidon-25/ 50 tab ( Bondane Pharma India).

Composition: Each tab contains 25mg / 50mg Clomipramine.

  • Clomidon-ST75 tab ( Bondane Pharma India).

Composition: Each tab contains 75mg Clomipramine.

  • Clomifril 10/25 ( Torrent India).

Composition: Each tab contains 10mg/25mg Clomipramine.

  • Clonil 10/25/50tab ( Intas India).

Composition: Each tab contains 10mg/25/mg/50mh Clomipramine

  • Clonil – SR 75 ( Intas India).

Composition: Each tab contains 75mg Clomipramine.

Pentobarbital

By M. Younus, BVSc, MVSc, SKUAST-K

Pentobarbital( Barbiturate)

  • Used for euthanasia  in dogs and cats.

MOA:

  •  Pentobarbital binds with GABA receptors in CNS , keeping chloride channels open for prolonged time.
  • This potentiate GABA effect.
  •  Pentobarbital also prevents glutamate receptors from binding with glutamate which is responsible for depolarization of nerves through opening of Ca channels.

Effects:

  •  Sedation and CNS depression.

Side effects:

  •  Excitement. 
  •  Slow breathing.
  •  Anxiety.
  •  Drowsiness.

Species:

  •  Dog and Cat.

Drug combinations:

  •  Pentobarbital + phenytoin potentiate the effect.

Dose:

 Euthanasia:

  • 28 -30 mg/kg IV on an empty stomach.
  •  63 mg/kg IV on full stomach.

 To control seizures: 

  • 2 to 15 mg/kg IV or 5 mg/kg/hr IV to effect.

Indication:

  •  As euthanizing agent.
  •  To control seizures.

Contraindication:

  •  Animals with porphyria.
  •  Seizures by lidocaine toxicity.
  •  Severe liver impairment.

Availability:

  • Nembutal 100ml inj vial ( CEVA) offered by Meds Pharma India.

Composition: Each ml contains 50mg Pentobarbital.

Phenobarbital

By M. Younus, BVSc, MVSc, SKUAST-K

Phenobarbital (long-acting barbituric acid derivative) 

  • Extra label drug.

MOA:

  • Phenobarbital  activates  gamma-aminobutyric acid (GABA)-A receptor, thereby mimicking the inhibitory actions of GABA in the brain.

Effects:

  •  Increased frequency of chloride channel openings.
  • Membrane hyperpolarization.
  •  Synaptic inhibition and decreased neuronal excitability. 
  • Inhibition of  glutamate induced depolarization.
  • Net effect is the  control of unexpected surge of neuron activity within  brain.

Side effects:

  • weakness.
  • Drowsiness.
  • Anxiety.
  • Restlessness.
  • Loss of coordination.
  • Increased thirst or appetite.
  • Weight gain.
  • Polyuria.
  •  Liver damage.

Species:

  • Dog.

Indication:

  • seizures.

Drug combinations:

  • Phenobarbital + Potassium bromide used in tandem with one another to achieve desired effect.

Dose:

  • 2-5mg/kg PO 8-12 hrly. 
  • The effect begins after period of two weeks.
  • Start with lower dose and increase in consultation with veterinarian.

Contraindication:

  • Anemia.
  • Liver disease.
  • Nephropathy.
  • Cardiopathy.
  • Addison’s disease.
  • Hypovolemia.
  • Hypoadrenocorticism.
  • Pulmonary disease.

Brands

Human brands:

  • Barbinol 30ml/100ml syrup( Human Antibiotic Pharmaceuticals India).

Composition: Each 5ml contains 20mg Phenobarbital. 

  • Emgard 15mg tab ( Medophram India).

Composition: Each tab contains 15mg Phenobarbital.

  • Barbee 30mg tab ( Ind-Swift).

Composition: Each tab contains 30mg Phenobarbital.

  • Beetal 30mg tab ( Intas India).

Composition: Each tab contains 30mg Phenobarbital.

  • Gardinal 30mg tab (Abbott India).

Composition: Each tab contains Phenobarbital.

  • Gardinal 100ml syrup (Abbott India).

Composition: Each 5ml contains 20mg Phenobarbital. 

  • Phenetone 30mg tab ( Cipla India).

Composition: Each tab contains 30mg Phenobarbital.

  • Epitan 30mg tab ( Reliance India).

Composition: Each tab contains 30mg Phenobarbital.

Imepitoin

By M. Younus, BVSc, MVSc, SKUAST-K

Imepitoin

  • Used both as anxiolytic and anticonvulsant drug.
  • Approved as a treatment for noise aversion in dogs
  • Effective in nonrefractory, newly diagnosed idiopathic epilepsy in dogs(study).
  • As an add-on medication to phenobarbital in dogs with drug-resistant idiopathic epilepsy(study)

MOA:

  • Glutamate spikes have been implicated in stroke; idiopathic epilepsy affecting the hippocampus and frontal cortex in humans, rodents, and cats; and behavioral pathologies involving impulsive components. 
  • Imepitoin is a partial gamma aminobutyric acid (GABA)-A agonist.
  • Imepitoin also blocks voltage-gated calcium channels in a dose-dependent manner and may stimulate the barbiturate binding site of the GABAA receptor.
  • These actions activate the GABAA receptor, stimulating inhibition of activity, and can counteract the excitatory effects of the amino acid glutamate.

Effects:

  • Anxiolytic and anticonvulsant effect.

Side effects :

  • Vomiting.
  • Polyphagia.
  • Sedation.
  • Ataxia lasting for days after initial 3-day treatment phase.

Species:

  • Dog

Dose:

  • 10 to 30 mg/kg PO BID depending upon problem.
  • 30 mg/kg twice daily to be given 2 days prior to a noise event and continuing through the end of the event.
  • For idiopathic epilepsy: 5 to 10 mg/kg PO q12h and increase by 50% to 100% weekly depending on degree of resolution.
  • For generalized anxiety disorder: 20 mg/kg PO BID.

Indication:

  • Idiopathic epilepsy.
  • Generalized anxiety disorder.
  • Prophylactic measure prior to a noise event.

Contraindication:

  • Hypersensitivity to any of the excipients of formulation.
  • liver/heart/renal problems.
  • Simultaneous use of proton pump inhibitors.

Brands

  • Pixion 100mg/400mg tab ( Boenhringer Ingelheum )-imported