Technical Information
M99 (Etorphine)

M99 (etorphine hydrochloride) was synthesised by Bentley & Hardy (1963) and is chemically related to morphine. When given subcutaneously, M99 is 1,000 to 80,000 times more potent than morphine as an analgesic. Its use for immobilising game animals results largely from its ability to cause catatonia at very low dose levels (for example, the total dose for a rhino may be as low as 5 mg). Because of the great risk involved to man and animal in handling this substance, the possession and use of M99 is strictly controlled by law in almost all countries. Novartis enforces this and ensures that M99 and M5050 is only supplied to registered veterinarians.

The approved generic name of this compound is etorphine hydrochloride, and the chemical name is 6,14-endoetheno – 7 a (1-(R)-hydroxy-1 methylbutyl)-tetrahydro-nororipavine hydrochloride.

M99 is chemically related to morphine. This compound was synthesised by Bentley & Hardy (1963). The acute pharmacology was described in detail by Blane, Bora, Fitzgerald and Lister (1967). In laboratory animals M99 resembles morphine by causing analgesia, catatonia, blockade of conditional reflexes, and anti-diuretic effect. It also resembles morphine by causing excitement in mice, cats and bradycardia and hypotension in rats, dogs, cats and monkeys. When given subcutaneously M99 is 1,000 - 80,000 times more potent than morphine as an analgesic, depending on the test situation. Its use for immobilising game animals results largely from its ability to cause catatonia at very low dose levels.

M5050

The approved generic name for this compound is diprenorphine, and the chemical name is N-cyclopropylmethyl-6, 14-endoetheno-7-(1-hydroxy-1-methylethyl)tetrahydro-nororipavine. It is a potent morphine antagonist with an action similar to nalorphine. Its potency, however, was stated by Bentley et al. (1965) to be up to 35 times greater than nalorphine and to have a duration of action two to three times as long. In game animals it produced a rapid and complete reversal of the immobilisation produced by M99. Although it appears that there may be some degree of species variation in the response in practice it has been found that a dosage ratio M5050 to M99 of 1:1 is perfectly satisfactory i.e. 1.3mg diprenorphine produces reversal of the immobilising action of 1mg etorphine.

Safety Precautions

1. Keep M99 and M5050 together.
2. Ensure that there is sufficient M5050 to reverse the effects of M99.
3. Load the M5050 syringe first and keep it to hand throughout the procedure.
4. Load the M99 syringe well clear of the patient or assisting persons.
5. Use a disposable syringe.
6. Discard empty M99/M5050 vials - never reuse containers for other drugs.
7. Always ensure that a syringe loaded with an appropriate antidote for human use is at hand (Narcan).
8. DON’T confuse different preparations.
9. DON’T use a syringe that has previously been used for M99 or any other drugs.
10. DON’T carry a syringe loaded with M99 in your pocket. Syringes loaded with M99 should carry a needle guard.

Further advice on handling Large Animal M99

1. Once the required dose of M99 has been withdrawn from the vial it is strongly recommended that the needle be removed from the syringe and discarded into a closed container. A sterile needle should then be inserted into the injection site and the syringe connected to it.
2. Wear gloves.
3. Do not pressurise the contents of the vial.
4. An eye and skin wash should be made available.
5. An assistant capable of giving an injection of reversing agent should be present whenever Large Animal M99 is used.
6. The veterinary surgeon should fully brief the assistant on the procedure and indicate whether M5050 is to be considered as an antidote in the event of personal accident.
7. To minimise risk of accident when injecting M99 i.v., the Portex Minivein or similar equipment can be used.
8. Immobilise only one animal at a time and keep it under constant supervision at all stages. In cases of respiratory failure, inject M5050 immediately and maintain artificial ventilation.

Accident Procedure

M99 is a very potent neuroleptanalgesic which is highly toxic in man. It causes dizziness, nausea and pinpoint pupils, followed by respiratory depression, lowered blood pressure, cyanosis and, in extreme cases, loss of consciousness and cardiac arrest.

If there is any danger that M99 may have been injected or absorbed, the following steps should be taken IMMEDIATELY!!!!! In case of:

1. Accidental injection (including needle scratch).
2. Splashing into eyes, mouth or nose.
3. Spillage on to the skin or immediate clothing.

BEFORE CALLING MEDICAL ASSISTANCE, INJECT A REVERSING AGENT. In case of 1) or 2), immediate washing with plenty of water may prevent significant absorption, but THIS SHOULD NEVER BE ASSUMED. THE DATA SHEET OR PACK LEAFLET SHOULD BE HANDED TO THE ATTENDING DOCTOR.

Reversing Agents

Inject 2-3mls Narcan (0.4mg/ml naloxone) preferably intravenously or alternatively intramuscularly, and repeat at intervals of 2 to 3 minutes until symptoms are reversed. In the event of Narcan being unavailable, or in a situation of extreme emergency, the following information is provided for possible guidance: Inject 0.1ml M5050 preferably intravenously or alternatively intramuscularly, but if the actual quantity of M99 injected or absorbed is known inject an equal quantity of M5050. If respiratory depression is not reversed, repeat the dose after 2 or 3 minutes. Recurrence of morphine-like effects may occur due to enterohepatic recycling. (M5050 may also induce a hallucinatory state). IT IS VITAL THAT ADEQUATE RESPIRATION AND HEARTBEAT BE MAINTAINED, IF NECESSARY BY MEANS OF ARTIFICAL RESPIRATION AND EXTERNAL HEART MASSAGE, UNTIL MEDICAL HELP ARRIVES.

Adequate respiration must be maintained by:

(a) Ensuring that the airway is clear by placing the patient in the recovery position removing dentures or any other oral obstruction, and

(b) applying artifical ventilation if breathing has stopped altogether. The mouth-to-mouth technique is usually the only one applicable in the circumstances.

Medical Assistance

Once the emergency measures have been undertaken as set out above, expert medical attention should be summoned immediately. Pending the transfer of the patient to medical care the supportive treatment to maintain the respiration and heartbeat should be continued as required. Respiratory arrest beyond 4 minutes may cause irreversible brain damage.

Emergency Pack

This must be carried by all users. It should contain explicit instructions as well as:

1. Tourniquet
2. 2ml plastic sterile syringes with 1_" 21g Needles.
3. At least 6 ampoules of NARCAN (Naxolone)

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