Cutaneous Trunci Muscle Research Articles

Subcutaneous infiltration of doxylamine on cutaneous analgesia in rats.

We aimed to evaluate the effect of doxylamine, a first generation antihistamine, as a local analgesic agent by comparing its effect to bupivacaine. After blocking the cutaneous trunci muscle reflex (CTMR) by subcutaneous injection of doxylamine, we assessed doxylamine's cutaneous analgesic effect in rats. The dose-related effect and duration of doxylamine on infiltrative cutaneous analgesia were compared with that of bupivacaine. We demonstrated that doxylamine, as well as the local anesthetic bupivacaine produced the cutaneous analgesic effects in a dose-related fashion. At the equipotent dose (50% effective doses (ED50)), the relative potency was bupivacaine (0.41 (0.36-0.48) mmol)> doxylamine (7.39 (6.91-7.91)mmol) (p<0.01). On an equipotent basis (ED25, ED50 and ED75), subcutaneous doxylamine resulted in greater duration of action (p<0.01) than bupivacaine at producing cutaneous analgesia. The result of this experiment indicated that doxylamine has the local anesthetic property less potent than bupivacaine, but its nociceptive block duration is longer than that of bupivacaine at an equianalgesic dose.

Evaluation of whole pork belly qualitative and quantitative properties using selective belly muscle parameters

The objective of this study was to identify parameters for the evaluation of pork belly quality (composition) and quantity (volume) and to develop regression equations that predict properties of whole pork belly. Through an image analysis of 648 bellies, newly characterized pork belly parameters were developed for evaluating pork belly quality and quantity. Importantly, the estimated muscle volume showed high positive correlation with the whole belly volume and the whole belly muscle percentage (r=0.458, and 0.654, respectively). Section 7 was identified as the best section for the evaluation of pork belly based on the muscle area in every vertebra. A stepwise regression showed that cutaneous trunci muscle (CTM) had an r2 of 0.624 in the model, and supplementation with the other muscles yielded an r2 of 0.784. Therefore, we propose that a prediction equation could be developed for a certain area in the belly for the evaluation of pork belly quantity and quality. The results could be applied to select breeding stock using techniques such as ultrasound with the aim of producing hogs with large as well as lean bellies.

Naloxone prolongs cutaneous nociceptive block by lidocaine in rats.

We aimed to investigate the local anesthetic properties of naloxone alone or as an adjunct for the local anesthetic lidocaine. After the block of the cutaneous trunci muscle reflex (CTMR) with drugsdelivery by subcutaneous infiltration, cutaneous nociceptive block was tested on the ratsꞌ backs. We demonstrated that naloxone, as well as lidocaine, elicited cutaneous analgesia dose-dependently. The relative potency in inducing cutaneous analgesia was lidocaine [22.6 (20.1 - 25.4) μmol/kg] > naloxone [43.2 (40.3 - 46.4) μmol/kg] (P<0.05). On an equianesthetic basis [50% effective dose (ED50 ), ED25 , and ED75 ], naloxone displayed a greater duration of cutaneous analgesic action than lidocaine (P<0.01). Coadministration of lidocaine (ED95 or ED50 ) and ineffective-dose naloxone (13.3μmol/kg) intensifies sensory block (P<0.01) with prolonged duration of action (P<0.001) compared with lidocaine (ED95 or ED50 ) alone or naloxone (13.3μmol/kg) alone on infiltrative cutaneous analgesia. The preclinical data showed that naloxone is less potent than lidocaine as an infiltrative anesthetic, but its analgesic duration was longer than that of lidocaine. Furthermore, naloxone prolongs lidocaine analgesia, acting synergistically for nociceptive block.

Mexiletine co-injected with clonidine increases the quality and duration of cutaneous analgesia in response to skin pinpricks in the rat.

The goal of the experimental design was to assess the cutaneous analgesic effect of mexiletine by co-injection with clonidine. The effect of nociceptive block was evaluated according to the inhibition of the cutaneous trunci muscle reflex (CTMR) in response to skin pinpricks in rats. The dose-related analgesic effect of mexiletine alone or mexiletine co-administrated with clonidine was constructed after subcutaneous injection. Subcutaneous injections of mexiletine elicited dose-related cutaneous analgesia. Compared with mexiletine (1.8μmol), adding clonidine to mexiletine (1.8μmol) solutions for skin nociceptive block potentiated and prolonged the action (p<0.01). Mexiletine (6μmol) combined with clonidine extended the duration of cutaneous analgesia when compared with mexiletine (6μmol) alone (p<0.01). Co-administration of clonidine increases the potency and extends the duration of cutaneous analgesia by mexiletine, and the minimal dose of clonidine to intensify the analgesic effect is 0.06μmol.

Isobolographic analysis of the cutaneous antinociceptive interaction between bupivacaine co-injected with serotonin in rats.

The aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception. The skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug-drug interactions were evaluated by isobologram. Subcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED50]), the relative potency was bupivacaine (0.43 [0.37-0.50] μmol)>serotonin (1.27 [1.15-1.40] μmol) (p<0.01). At the equi-anesthetic doses (ED75, ED50 and ED25), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception. The preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine+serotonin than bupivacaine alone.

Synergistic Effects of Serotonin or Dopamine Combined With Lidocaine at Producing Nociceptive Block in Rats.

The purpose of this experiment was to investigate the interactions of the local anesthetic lidocaine combined with an agent (serotonin or dopamine) as infiltrative anesthetics. Cutaneous analgesia was characterized by the blockade of the cutaneous trunci muscle reflex following 6 skin pinpricks on the rat back. Serotonin or dopamine at producing cutaneous analgesia in a dosage-dependent fashion was compared with lidocaine. Drug-drug interactions were calculated using the isobolographic analysis. We revealed that serotonin, dopamine, and lidocaine provoked dose-related cutaneous analgesic effects. On the 50% effective dose basis, the rank of drugs' potency was found to be serotonin (1.70 [1.56-1.85] μmol) > lidocaine (5.18 [4.67-5.75] μmol) > dopamine (43.0 [40.9-45.2] μmol) (P < 0.01). At doses equivalent to their 25%, 50%, and 75% effective doses, serotonin or dopamine elicited a longer duration of action than lidocaine (P < 0.01) on producing cutaneous analgesia. Coadministration of serotonin or dopamine with lidocaine produced a synergistic effect. The preclinical data showed that serotonin and dopamine produce dose-related cutaneous analgesic effects as an infiltrative anesthetic. Serotonin has a better potency with a much longer duration of action compared with lidocaine at provoking cutaneous analgesia. Serotonin or dopamine as an adjuvant increases the quality of lidocaine in cutaneous analgesia.

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92–2.09] μmol/kg) greater than dopamine (190 [181–203] μmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect.

Clonidine as an adjuvant for propranolol enhances its effect on infiltrative cutaneous analgesia in rats

Clonidine prolongs duration of analgesia when used as an adjunct to local anesthetics for infiltrative cutaneous analgesia, and propranolol produces local anesthesia. The purpose of the experiment was to evaluate clonidine as an adjuvant for propranolol on the quality and duration of cutaneous analgesia. A rat model of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick was employed to evaluate the cutaneous analgesic effect of propranolol combined with clonidine. The long-lasting local anesthetic bupivacaine was used as control. Cutaneous analgesia elicited by propranolol and bupivacaine was dose-dependent, and both propranolol (9.0μmol) and bupivacaine (1.8μmol) produced 100% nociceptive blockade. On an 50% effective dose (ED50) basis, the relative potency was bupivacaine [0.48 (0.42–0.55) μmol] greater than propranolol [2.27 (1.98–2.54) μmol] (p<0.01). Subcutaneous saline and clonidine (0.12μmol) did not produce cutaneous analgesia. The mixture of an ineffective-dose clonidine (0.12μmol) and a drug (propranolol or bupivacaine) at ED50 or ED95 increased the potency and extended the duration at producing cutaneous analgesia. The resulting data demonstrated that propranolol is less potent than bupivacaine as an infiltrative anesthetic. Clonidine as an adjuvant for propranolol or bupivacaine has a significant peripheral action in increasing the depth and duration of action on infiltrative cutaneous analgesia.

A New Flap Model in the Treatment of Non-Healing Elbow Wounds in Dogs: The Island Arterial Composite Flap Comprising the Skin Originating from the Thoracodorsal Artery, the Cutaneous Trunci Muscle and Fascia of the Latissimus Dorsi Muscle

In the treatment of wounds with tissue loss in the elbow region, despite the most frequently used method being the tube flap of thoracodorsal artery origin, this method has the disadvantages of necrosis, opening of sutures and tension. The aim of this study is to present the results of the island arterial composite flap, containing the skin of the thoracodorsal area, the cutaneous trunci muscle and fascia of the latissimus dorsi muscle, for the reconstruction of chronic wounds in the elbow region. The material of the study consisted of 14 dogs with either non-healing wounds or wounds with tissue loss in the elbow region. Firstly, debridement of the elbow defect was carried out. Next, an elliptical incision depending on the size of the defect was made in the thoracodorsal skin. Once the thoracodorsal artery and its pedicle were exposed, this was passed through the tunnel formed in the axillary region and placed over the debrided defect in the elbow region. It was sutured using non-absorbable monofilament suture material and simple interrupted sutures and the results were evaluated. In conclusion, the skin originating from the thoracodorsal artery, muscle and fascia island artery flap may be an effective method in the reconstruction of wounds in the elbow region.

The Addition of Epinephrine to Proxymetacaine or Oxybuprocaine Solution Increases the Depth and Duration of Cutaneous Analgesia in Rats.

The aim of this experiment was to investigate the interaction between epinephrine and 2 local anesthetics (proxymetacaine or oxybuprocaine) using subcutaneous injections under the hairy skin, thereby simulating infiltration blocks. Using a rat model of cutaneous trunci muscle reflex in response to local skin pinpricks, the anesthetic properties of proxymetacaine and oxybuprocaine alone and in combination with epinephrine as an infiltrative anesthetic were tested. Isobolographic analysis was used for the analgesic interactions between adjuvant epinephrine and the local anesthetics. Lidocaine was used as a control group. Oxybuprocaine, proxymetacaine, and lidocaine elicited a dose-dependent block to pinpricks. On the 50% effective dose (ED50) basis, their relative potencies were proxymetacaine [0.126 (0.113-0.141) μmol] greater than oxybuprocaine [0.208 (0.192-0.226) μmol] greater than lidocaine [6.331 (5.662-7.079) μmol] (P < 0.01 for each comparison). On an equipotent basis (ED25, ED50, and ED75), sensory block duration elicited by oxybuprocaine or proxymetacaine was greater than that elicited by lidocaine (P < 0.01). Coadministration of proxymetacaine, oxybuprocaine, or lidocaine with epinephrine produced a synergistic analgesic effect and prolonged the cutaneous analgesic effect. After adding epinephrine, oxybuprocaine was much faster, reaching its maximal blockade, than proxymetacaine or lidocaine (P < 0.01). We concluded that proxymetacaine and oxybuprocaine were more potent and produced greater duration of nociceptive block than lidocaine. The use of epinephrine augmented the potency and prolonged the duration of proxymetacaine, oxybuprocaine, and lidocaine as an infiltrative anesthetic.

Subcutaneous l-tyrosine elicits cutaneous analgesia in response to local skin pinprick in rats

The purpose of the study was to estimate the ability of l-tyrosine to induce cutaneous analgesia and to investigate the interaction between l-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with l-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug–drug interaction was analyzed by using an isobolographic method. We showed that both l-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88–5.38]μmol)>l-tyrosine (39.1 [36.5–41.8]μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by l-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with l-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that l-tyrosine elicits the local/cutaneous analgesia, and the interaction between l-tyrosine and lidocaine is additive. l-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding l-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone.

Propranolol combined with dopamine has a synergistic action in intensifying and prolonging cutaneous analgesia in rats.

The purpose of the experiment was to assess interactions of dopamine with propranolol as an infiltrative anesthetic. After injecting the rats with four doses of drugs subcutaneously, the cutaneous analgesic effect of propranolol was compared with dopamine through the blockade of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick. Drug-drug interactions were examined via an isobolographic analysis. We demonstrated that the action of propranolol and dopamine was dose dependent to skin infiltrative analgesia. On the ED(50) (50% effective dose) basis, the rank of drug potency was propranolol (11.3 [10.6-12.2]μmol) > dopamine (195 [188-205]μmol) (p < 0.001). At the equi-anesthetic doses (ED(25), ED(50), ED(75)), the block duration caused by dopamine was equal to that caused by propranolol. Coadministration of dopamine and propranolol exhibited a synergistic effect on infiltrative cutaneous analgesia. The preclinical data showed that dopamine produced a lesser potency but a comparable duration of cutaneous analgesia compared to propranolol. Adding dopamine to propranolol potentiated and prolonged propranolol's cutaneous analgesic effect.

Estimation of Genetic Parameters for Pork Belly Components in Yorkshire Pigs.

This study was conducted to estimate the genetic parameters for pork belly traits and muscles in Yorkshire pigs. Each pork belly was cut into nine parts perpendicular to the thoracic vertebrae (6th to 14th). Traits of belly muscles including the deep pectoral, latissimus dorsi, cutaneous trunci, rectus abdominis, external and internal abdominal oblique from 382 purebred pigs were recorded and analyzed using SAS Package (9.1) and Derivative-free restricted maximum likelihood methods. Heritability estimates for belly traits ranged from 0.27 to 0.49, while they were 0.12 to 0.66 for belly muscles. Moderate to high heritability estimates were noted in belly weight (0.33), belly length (0.28), and belly width (0.49). In belly muscles, the latissimus dorsi and deep pectoral, which are located only in the 6th to 9th vertebrae sections, were found to have heritability estimates ranging from 0.21 to 0.29 and 0.23 to 0.35, respectively. Strong heritability estimates were observed in the 7th to 13th sections of cutaneous trunci muscle ranging from 0.42 to 0.66. Genetic correlations of latissimus dorsi m. with belly length were positive (0.50), while cutaneous trunci m. with belly weight also revealed a positive relationship that ranged from 0.35 to 0.47. The estimated genetic parameters indicate that belly weight can be improved by genetic selection. Differences in the levels of heritability occurred among various parameters of Yorkshire pork belly, which should be considered when performing selection to improve pork belly quality. Moreover, these results can provide valuable information that can be used as the basis for further investigations to improve pork belly.

Dextrorphan for Prolonged Skin Infiltration Anesthesia by Adding Epinephrine in Rats

Dextrorphan could be a local anesthetic, while adding epinephrine to the local anesthetics prolonged their duration of action. Here we investigated whether epinephrine as adjuvant could prolong the local anesthetic effect of dextrorphan. The cutaneous analgesic effect of the addition of epinephrine (5 μg/mL) to dextrorphan was assessed in rats following the blockade of cutaneous trunci muscle reflex through subcutaneous injection of drugs. We showed that subcutaneous dextrorphan elicited dose-dependent cutaneous analgesia. Co-administration of epinephrine (5 􀀁g/mL) with dextrorphan at 50% effective dose (ED50) or ED95 had a longer duration than dextrorphan (ED50 or ED95) alone, respectively. This study indicated for the first time that the mixtures of epinephrine with dextrorphan increased the duration as an infiltrative anesthetic.

Clonidine intensifies memantine cutaneous analgesia in response to local skin noxious pinprick in the rat

BackgroundThe purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia. MethodsCutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine. ResultsOn the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95–4.18)μmol]>lidocaine [5.81 (5.70–5.98)μmol] (p<0.01). Clonidine at a dose of 0.12μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine. ConclusionsOur resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine.

Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats

The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95–2.21)μmol/kg]>propranolol [9.21 (9.08–9.42)μmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012μmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012μmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012μmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.

Co-administration of memantine with epinephrine produces a marked peripheral action in intensifying and prolonging analgesia in response to local skin pinprick in rats

The purpose of this study was to examine the effect of epinephrine as adjuvant for memantine or lidocaine as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we evaluated the effects of adding epinephrine to memantine or lidocaine on infiltrative cutaneous analgesia. Lidocaine, a known local anesthetic, was used as control. We found that epinephrine, memantine, and lidocaine produced a dose-dependent local anesthetic effect as infiltrative cutaneous analgesia. On a 50% effective dose (ED50) basis, the relative potencies were epinephrine [0.012 (0.006–0.020)μmol]>memantine [4.010 (3.311–4.988)μmol]>lidocaine [6.177 (5.333–7.218)μmol] (P<0.05 for each comparison). Mixtures of epinephrine (2.7nmol or 13.7nmol) with drugs (memantine or lidocaine) at ED50 or ED95, respectively, enhanced the potency and prolonged the duration of action on infiltrative cutaneous analgesia. Intraperitoneal injection of co-administration of drugs (memantine or lidocaine) at ED95 with epinephrine (13.7nmol) produced no cutaneous analgesia (data not shown). Epinephrine, memantine, and lidocaine were shown to have local anesthetic effects as infiltrative cutaneous analgesia. Epinephrine increased the duration and potency of memantine and lidocaine as an infiltrative anesthetic.

Diphenhydramine produces local cutaneous analgesia in response to dorsal skin noxious stimuli in the rat

Although diphenhydramine has been shown to produce longer duration of spinal block than lidocaine, few studies disclose its skin infiltrative anesthesia when compared with a long-lasting local anesthetic, bupivacaine. The purpose of this study was to investigate whether diphenhydramine elicited cutaneous analgesia in comparison with bupivacaine. After inhibition of cutaneous trunci muscle reflex via subcutaneous injection of drugs in rats, we examined the local anesthetic effect of diphenhydramine and bupivacaine as infiltrative cutaneous analgesia in a dose-dependent fashion. We showed that diphenhydramine, as well as bupivacaine displayed a dose-dependent cutaneous analgesia in response to dorsal cutaneous noxious stimuli. The relative potency (50% effective dose) was bupivacaine (0.023 [0.013-0.035]%)>diphenhydramine (0.078 [0.068-0.091]%; P<0.001). On an equipotent basis, diphenhydramine had a similar duration of action to bupivacaine. Neither local injection of saline nor intraperitoneal administration of a large dose of diphenhydramine or bupivacaine produced cutaneous analgesia (data not shown). We conclude that diphenhydramine is less potent than bupivacaine at producing cutaneous analgesia. At equipotent doses for infiltrative cutaneous analgesia, the duration of action of diphenhydramine is equal to that of bupivacaine.

Rimantadine and 2-adamantanamine elicit local anesthesia to cutaneous nociceptive stimuli in a rat model

The aim of this study was to investigate infiltrative cutaneous anesthesia of 2-adamantanamine and rimantadine. After subcutaneous injections of drugs in rats, the blockade of cutaneous trunci muscle reflex by 2-adamantanamine and rimantadine was evaluated. Lidocaine, a common local anesthetic, was used as control. We showed that rimantadine and 2-adamantanamine as well as the local anesthetic lidocaine produced infiltrative anesthesia of skin in a dose-dependent fashion. Saline (vehicle) group displayed no cutaneous anesthesia. The relative potency of these drugs was rimantadine [23.8 (21.1-26.8)]=lidocaine [26.4 (22.7-30.6)]>2-adamantanamine [64.6 (55.0-75.9)] (P<0.01). On an equianesthetic basis [25% effective dose (ED25 ), ED50 , and ED75 ], rimantadine and 2-adamantanamine had longer duration of action than lidocaine (P<0.05). Neither local injection of saline nor intraperitoneal administration of a large dose of drugs elicited cutaneous anesthesia (data not shown). These data demonstrated for the first time that rimantadine had a similar potent and longer duration of skin infiltrative anesthesia than did lidocaine, whereas 2-adamantanamine had a less potency but longer duration of cutaneous anesthesia than did lidocaine.

Cutaneous analgesia after subcutaneous injection of memantine and amantadine and their systemic toxicity in rats

The purpose of the study is to find subcutaneous equianalgesic doses of memantine, amantadine and bupivacaine and use these doses to quantify the cardiovascular and central nervous system toxicity of these agents after intravenous administration. Memantine, amantadine and bupivacaine, a local anesthetic, in a dose-related fashion were determined for cutaneous analgesia by a block of the cutaneous trunci muscle reflex in rats, and equipotent doses were calculated. Following rapid intravenous infusion of equianalgesic bupivacaine, memantine, amantadine and saline (vehicle) in rats, we observed the onset time of seizure, apnea and impending death, and monitored mean arterial blood pressure and heart rate. Memantine and amantadine elicited dose-dependent cutaneous analgesia. At the 50% effective dose (ED50), the rank of potencies was bupivacaine [1.8 (1.7–2.0)]>memantine [19.1 (17.6–21.8)]>amantadine [36.1 (32.0–40.3)] (P<0.05). On ED25, ED50 and ED75 basis, the duration caused by bupivacaine was similar to that caused by memantine or amantadine. At equianalgesic doses, the infusion time of memantine or amantadine required to induce seizure, impending death, and apnea was longer than that of bupivacaine during rapid intravenous infusion (P<0.01). The decreasing slope in mean arterial blood pressure and heart rate was slower with memantine and amantadine when compared with bupivacaine at equivalent doses (P<0.01). Our data showed that memantine and amantadine (i) were equal to bupivacaine at producing durations of cutaneous analgesia but (ii) were less likely than bupivacaine to cause cardiovascular and central nervous system toxicity.