α2-adrenoceptor agonist [1]

In Welsh mountain ponies, romifedine (80 μg/kg; intravenously administered once) causes drowsiness and a marked increase in sag [1]. When given intravenously every seven days, romifidine (40, 80, and 120 mg/kg) sedates horses more deeply and fleetingly than detomidine [2].

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At doses of 40 μg/kg and 80 μg/kg intravenously, romifidine produced dose-dependent sedation in horses, characterized by lowered head, drooping of lower lip, slight closing of eyes, muscle twitches, slight head jerks, and ataxia. The higher dose (80 μg/kg) produced a longer duration of action and residual sedation lasting up to 200 minutes (average 160 minutes). [1]

- Head height (distance from muzzle to floor) was significantly reduced. Romifidine 80 μg/kg produced significantly greater head drooping during the 45-90 min time period compared to other treatments. Romifidine produced less head lowering than xylazine (1 mg/kg) or detomidine (20 μg/kg). [1]

- Ataxia: Both doses of romifidine produced similar ataxia scores statistically, though subjectively horses showed greater ataxia for longer periods after the higher dose (80 μg/kg). Lower dose romifidine (40 μg/kg) produced ataxia lasting up to 30 minutes, while higher dose produced ataxia lasting up to 1 hour. Romifidine 40 μg/kg was not significantly different from detomidine 10 μg/kg in onset, degree, and duration of ataxia. [1]

- Response to imposed stimuli (tactile stimulation of ears, front and back feet) showed significant reduction at 5 and 10 minutes after romifidine administration. Response to visual and auditory stimulation showed no relationship to treatment. [1]

- Heart rate fell rapidly and was significantly depressed within 1 minute after romifidine injection. For the higher dose (80 μg/kg), heart rate remained significantly depressed for the duration of the study (90 minutes). Bradycardia was frequently accompanied by atrioventricular heart block. [1]

- Penile prolapse was noted 30 to 90 minutes after romifidine injection (later than xylazine and detomidine, which showed first signs at 5-30 minutes). Sweating and urination occurred with equal frequency as other drugs. [1]

- Residual sedation after romifidine: After removal from stocks, horses given 40 μg/kg romifidine were considered quiet, with residual sedation lasting up to 210 minutes. Horses given 80 μg/kg romifidine showed residual sedation present for up to 200 minutes (average 160 minutes), standing quietly without moving, occasionally scuffing toes, with decreased responses to handling and environmental stimulation. [1]

Five horses (four Welsh Mountain Ponies weighing 270-365 kg, and one Thoroughbred horse weighing 520 kg) were used. Animals were kept at grass with no supplementary feeding, housed overnight before and after sedation with hay and water ad libitum. [1]

- A Latin-square design with five different drug administrations was used, including romifidine 40 μg/kg intravenously and romifidine 80 μg/kg intravenously. Treatments were separated by at least six days. A blind trial was used: injection was made by a person other than the evaluator. [1]

- Animals were placed in wooden stocks where they stood quietly unrestrained. Prior to injection, an 18-gauge catheter was placed into the jugular vein. Animals were observed continuously for 90 minutes, during which measurements (ataxia score, head height from floor to muzzle, response to imposed stimuli, heart rate and rhythm via electrocardiogram) were taken. After 90 minutes, animals were walked from the stocks and subjective assessments were made at 15-30 minute intervals until recovery was complete. [1]

- Ataxia was scored on a scale of 0-3 (0: no change; 1: stable but swaying slightly; 2: swaying and leaning on stocks; 3: swaying, leaning, hind legs crossed, forelegs buckled). Head height was measured as distance from floor to muzzle. Imposed stimuli (touching ear pinnae, front and back feet with finger/pen tip; clapping hands behind animal; waving cloth towards head) were scored 0-3 (0: no response; 1: slow/hesitant; 2: medium speed; 3: marked/rapid). [1]

Bradycardia: Heart rate fell rapidly within 1 minute after romifidine injection, with minimum heart rates reaching 20 beats per minute at 5 minutes post-administration. Atrioventricular heart block occurred at the time of maximum bradycardia. [1]

- Penile prolapse was noted after romifidine administration, first observed 30 to 90 minutes after injection. [1]

- Sweating (varying from damp coat to profuse sweating) was noted equally across groups, considered more related to environmental temperature. Urination was noted with equal frequency, most frequently occurring after 45 minutes from drug administration. [1]

[1]. A comparison of the sedative effects of three alpha 2-adrenoceptor agonists (romifidine, detomidine and xylazine) in the horse. J Vet Pharmacol Ther. 1992 Jun;15(2):194-201.

[2]. Sedative and analgesic effects of detomidine and romifidine in horses. Vet Rec. 1995 Apr 1;136(13):324-7.

Romifedipine is a veterinary drug primarily used as a sedative in large animals (most commonly horses). It is also less commonly used in many other animals. Its chemical structure is very similar to clonidine, but romifedipine is not approved for human use. See also: Romifedipine hydrochloride (salt form).

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Romifidine (2-[(2-bromo-6-fluorophenyl)imino]imidazolidine monohydrochloride) is a potent and selective α2-adrenoceptor agonist used for sedation and analgesia in the horse. [1]

- Romifidine produces central nervous system effects of sedation, analgesia, bradycardia, respiratory depression, mild hypotension, and reduction in circulating antidiuretic hormone; peripheral effects include vasoconstriction leading to transient hypertension and reduction in gut activity. Its actions and adverse effects are typical of α2-adrenoceptor agonists and similar to xylazine and detomidine. [1]

- At 40 μg/kg intravenously, romifidine appeared equipotent to 10 μg/kg detomidine; at 80 μg/kg intravenously, it appeared similar in potency to 1 mg/kg xylazine and 20 μg/kg detomidine. The changes in heart rate were similar for all drug regimes. Romifidine produces less lowering of the head during sedation and a longer period of residual sedation compared to detomidine and xylazine. [1]

C9H9N3FBR

258.09026

256.996

65896-16-4

Romifidine hydrochloride;65896-14-2

71969

White to off-white solid powder

1.7±0.1 g/cm3

303.2±52.0 °C at 760 mmHg

110 °C

137.2±30.7 °C

0.0±0.6 mmHg at 25°C

1.662

1.02

2

2

2

14

234

0

KDPNLRQZHDJRFU-UHFFFAOYSA-N

InChI=1S/C9H9BrFN3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)

N-(2-bromo-6-fluorophenyl)-4,5-dihydro-1H-imidazol-2-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~968.65 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)