Mepivacaine: its pharmacological effects and their relationship to analytical findings in the horse

Abstract

Mepivacaine is a local anaesthetic drug that is widely used in equine medicine and is classified by the Association of Racing Commissioners International (ARCI) as a Class 2 foreign substance that may cause regulators to impose significant penalties if residues are identified in post-race urine samples. Therefore, an analytical/pharmacological database was developed for this agent and its metabolites. Using an abaxial sesamoid local anaesthetic model, it was determined that the highest no-effect dose (HNED) for its local anaesthetic effect was 2 mg. Using enzyme-linked immunosorbent assay (ELISA) screening, it was determined that subcutaneous (s.c.) administration of the HNED of mepivacaine to eight horses yielded a peak urinary concentration of apparent mepivacaine of 63 ng/mL 2 h after injection. The major identified metabolite recovered from equine urine after dosing with mepivacaine is 3-hydroxymepivacaine. Therefore, 3-hydroxymepivacaine was synthesized, purified and characterized, and a quantitative mass spectrometric method was developed for this metabolite as isolated from horse urine. Following subcutaneous injection of the HNED of mepivacaine, the concentration of 3-hydroxymepivacaine recovered from horse urine reached a peak of about 64.6 ng/mL at 4 h after administration as measured by GC/MS. The concentration of mepivacaine or its metabolites after administration of a HNED dose are detectable by mass spectral techniques. Within the limits of this research, the study suggests that recovery of concentrations less than about 65 ng/mL of 3-hydroxymepivacaine from post-race urine samples may not be associated with a recent LA effect of mepivacaine.

The use of sedatives, analgesic and anaesthetic drugs in the horse: An electronic survey of members of the American Association of Equine Practitioners (AAEP)

“…Respondents used the local anaesthetics lidocaine (Harkins et al . 1998) and mepivacaine (Harkins et al . 1999a) with equal frequency despite the fact that mepivacaine is approved for use in horses and lidocaine is not.…”

Ropivacaine in the horse: its pharmacological responses, urinary detection and mass spectral confirmation

“…The synthesis of 3‐hydroxyropivacaine from ropivacaine was analogous to our previously reported syntheses of 3‐hydroxylidocaine (Harkins et al ., 1998), 3‐hydroxymepivacaine (Harkins et al ., 1999c) and 3‐hydroxybupivacaine (Harkins et al ., 1999b). Nitration of ropivacaine under classic conditions (mixture of concentrated sulfuric acid and nitric acid) resulted in the formation of 3‐nitroropivacaine, which was reduced with zinc dust in 50% acetic acid to produce 3‐aminoropivacaine in high yield.…”

Mepivacaine local anaesthetic duration in equine palmar digital nerve blocks

“…Mepivacaine hydrochloride produces conduction blockade in sensory neurons by slowing sodium influx into cells (Altman et al 1985). The resulting local anaesthetic effect has a rapid onset of action, which is advantageous when perineural analgesia is used as an adjunct in lameness diagnosis (Harkins et al 1999). A palmar digital nerve block is a useful tool to assess and localise lameness to the palmar aspect of the foot.…”

“…Local anaesthetic duration of procaine, tetracaine, lidocaine, mepivacaine and bupivacaine have been compared in studies involving rat sciatic nerve blocking procedures (Leblanc 1990;Dyhre et al 1997) and in human studies (Moore et al 1970). Previous reports have examined the effects and duration of mepivacaine in equine intra-articular spaces (Dyson and Kidd 1993;Andreen et al 1994;Gough et al 2002), the epidural space (Skarda et al 1984) and systemically (Harkins et al 1999). Knowledge of the duration of effect would provide valuable information when performing subsequent, additional blocks, especially if performed on different limbs.…”

“…Knowledge of the duration of effect would provide valuable information when performing subsequent, additional blocks, especially if performed on different limbs. To evaluate the effects and duration of the anaesthetic, previous studies have used observation (Pleasant et al 1997), motion analysis (Keegan et al 1997), superficial and deep muscular pinprick stimulations (Skarda and Muir 1982), or serum (Skarda et al 1984) and urine (Harkins et al 1999) mepivacaine concentrations. Lameness and the effectiveness of a nerve block are difficult to evaluate objectively by observation (Keegan et al 1998).…”