Biomedical subjects

M Burrows

Publications and source records attributed to M Burrows.

At least 37 records · Page 2Linked to original sources

PubMed1995

Hysteresis reduction in proprioception using presynaptic shunting inhibition.

1. The tonic responses of angular-position-sensitive afferents in the metathoracic chordotonal organ of the locust leg exhibit much hysteresis. For a given joint angle, the ratio of an afferent's tonic firing rate after extension to its firing rate after flexion (or vice versa) is typically between 1.2:1 and 3:1 but can be as large as 10:1. Spiking local interneurons, that receive direct inputs from these afferents, can, by contrast, exhibit much less hysteresis (between 1.1:1 and 1.2:1). We tested the hypothesis that presynaptic inhibitory interactions between afferent axons reduces the hysteresis of postsynaptic interneurons by acting as an automatic gain control mechanism. 2. We used two kinds of neural models to test this hypothesis: 1) an abstract nonspiking neural model in which a multiplicative, shunting term reduced the "firing rate" of the afferent and 2) a more realistic compartmental model in which shunting inhibition presynaptically attenuated the amplitude of the action potentials reaching the afferent terminals. 3. The abstract neural model demonstrated the automatic gain control capability of a network of laterally inhibited afferent units. A postsynaptic unit, which was connected to the competitive network of afferents, coded for joint angle without saturating as the strength of the afferent input increased by two orders of magnitude. This was possible because shunting inhibition exactly balanced the increase in the excitatory input. This compensatory mechanism required the sum of the excitatory and inhibitory conductances to be much larger than the leak conductance. This requirement suggested a graded weighting scheme in which the afferent recruited first (i.e., at a small joint angle) received the largest inhibition from each of the other afferents because of the lack of active neighbors, and the afferent recruited last (i.e., at a large joint angle) received the least inhibition because all the other afferents were active. 4. The compartmental model demonstrated that presynaptic shunting inhibition between afferents could decrease the average synaptic conductance caused by the afferents onto the spiking interneuron, thereby counterbalancing the afferents' large average firing rates after movements in the preferred direction. Therefore the total postsynaptic input per unit time did not differ much between the preferred and nonpreferred directions.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1995

Action of locust neuromodulatory neurons is coupled to specific motor patterns.

1. Many muscles of the locust are supplied by dorsal unpaired median neurons (DUM neurons) that release octopamine and alter the contractions caused by spikes in motor neurons. To determine when these neuromodulatory neurons are normally activated during behaviour, intracellular recordings were made simultaneously from them and from identified motor neurons during the specific motor pattern that underlies kicking. A kick consists of a rapid and powerful extension of the tibia of one or both hind legs that is produced by a defined motor pattern. Only 3 identified DUM neurons of the 20 in the metathoracic ganglion spike during a kick, and they supply muscles involved in generating the kick. Their spikes occur in a distinctive and repeatable pattern that is closely linked to the pattern of spikes in the flexor and extensor tibiae motor neurons. When the extensor and flexor muscles cocontract, these three DUM neurons produce a burst of spikes at frequencies that can rise to 25 Hz, and with the number of spikes (3-15) related to the duration of this phase of the motor pattern. The spikes stop when the flexor muscle is inhibited and therefore before the tibia is extended rapidly. The other DUM neurons which supply muscles that are not directly involved in kicking are either inhibited or spike only sporadically. 2. The activation of a specific subset of DUM neurons during kicking may thus be timed to influence the action of the muscles that participate in this movement and appear to be controlled by the same circuits that determine the actions of the participating motor neurons. These modulatory neurons thus have specific individual actions in the control of movement.

Animals↗

PubMed1995

Central connections of sensory neurones from a hair plate proprioceptor in the thoraco-coxal joint of the locust.

The hair plate proprioceptors at the thoraco-coxal joint of insect limbs provide information about the movements of the most basal joint of the legs. The ventral coxal hair plate of a middle leg consists of group of 10-15 long hairs (70 microns) and 20-30 short hairs (30 microns). The long hairs are deflected by the trochantin as the leg is swung forward during the swing phase of walking, and their sensory neurones respond phasically during an imposed deflection and tonically if the deflection is maintained. Selective stimulation of the long hairs elicits a resistance reflex that rotates the coxa posteriorly and is similar to that occurring at the transition from the swing to the stance phase of walking. The motor neurones innervating the posterior rotator and adductor coxae muscles are excited, and those to the antagonistic anterior rotator muscle are inhibited. By contrast, selective stimulation of the short hairs leads only to a weak inhibition of the anterior rotator. The excitatory effects of the long hairs are mediated, in part, by direct connections between their sensory neurones and particular motor neurones. A spike in a sensory neurone elicits a short-latency depolarising postsynaptic potential (PSP) in posterior rotator and adductor motor neurones whose amplitude is enhanced by hyperpolarising current injected into the motor neurone. When the calcium in the saline is replaced with magnesium, the amplitude of the PSP is reduced gradually, and not abruptly as would be expected if an interneurone were interposed in the pathway. Several sensory neurones from long hairs converge to excite an individual motor neurone, evoking spikes in some motor neurones. The projections of the sensory neurones overlap with some of the branches of the motor neurones in the lateral association centre of the neuropile. It is suggested that these pathways would limit the extent of the swing phase of walking and contribute to the switch to the stance phase in a negative feedback loop that relieves the excitation of the hairs by rotating the coxa backwards.

Animals↗

PubMed1995

Proprioceptive sensory neurons of a locust leg receive rhythmic presynpatic inhibition during walking.

Mechanosensory neurons from a proprioceptor (the femoral chordotonal organ) signal the movements and positions of the femorotibial joint of a locust leg. Intracellular recordings from these neurons during walking show that their spikes are superimposed on a depolarizing synaptic input generated near their output terminals in the CNS. The depolarization consists of a rhythmic synaptic input at each step, and a sustained input that begins before walking commences. In different sensory neurons, which signal particular features of the movement, the rhythmic depolarization occurs at distinct times during either the swing or stance phases of the step cycle. The depolarizing input is timed to coincide with the greatest spike response of a sensory neuron. The input is associated with a conductance change, appears to reverse just above resting potential, and thus has similar properties to the presynaptic inhibition in these same neurons during imposed joint movements (Burrows and Laurent, 1993; Burrows and Matheson, 1994). Three sources could contribute to these inputs: (1) interactions between sensory neurons of the same receptor signaling the same movement, (2) signals from different receptors in the same leg and other legs, and (3) outputs of central neurons involved in generating walking. When the leg, whose movements the sensory neurons signal is removed, both the sustained and rhythmic synaptic inputs persist. Sensory neurons in isolated ganglia treated with pilocarpine are also depolarized in phase with a rhythmic pattern expressed in leg motor neurons, indicating that central neurons must contribute. The maintained synaptic input to the terminals means that the overall effectiveness of the sensory spikes in evoking EPSPs in postsynaptic neurons will be reduced during walking, and the rhythmic component means that the spikes from particular sensory neurons will be further reduced at particular phases of the step cycle that they signal best.

Animals↗

PubMed1994

Processing of mechanosensory information from gustatory receptors on a hind leg of the locust.

Gustatory receptors (basiconic sensilla) on the legs of the desert locust, Schistocerca gregaria, are innervated by chemosensory afferents and by a mechanosensory afferent. We show, for the first time, that these mechanosensory afferents form an elaborate detector system with the following properties: 1) they have low threshold displacement angles that decrease with increasing stimulus frequency in the range 0.05-1 Hz, 2) they respond phasically to deflections of the receptor shaft and adapt rapidly to repetitive stimulation, 3) they encode the velocity of the stimulus in their spike frequency and have velocity thresholds lower than 1 degree/s, and 4) they are directionally sensitive, so that stimuli moving proximally towards the coxa elicit the greatest response. The mechanosensory afferents, but not the chemosensory afferents, make apparently monosynaptic connections with spiking local interneurones in a population with somata at the ventral midline of the metathoracic ganglion. They evoke excitatory synaptic potentials that can sum to produce spikes in the spiking local interneurones. Stimulation of the single mechanosensory afferent of a gustatory receptor can also give rise to long lasting depolarizations, or to bursts of excitatory postsynaptic potentials in the interneurones that can persist for several seconds after the afferent spikes. These interneurones are part of the local circuitry involved in the production of local movements of a leg. The mechanosensory afferents from gustatory receptors must, therefore, be considered as part of the complex array of exteroceptors that provide mechanosensory information to these local circuits for use in adjusting, or controlling locomotion.

Adaptation, Physiological↗

PubMed1994

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Ascites↗

PubMed1994

Activity-dependent structural dynamics of insect sensory fibers.

This report analyses the role of neuronal activity in shaping the axonal arborizations of sensory neurons from individually identified filiform hairs on the prosternum of locusts (Locusta migratoria), and their connections with a pair of identified interneurons (A4I1). Afferents from lateral filiform hairs terminate in the ipsilateral neuropil and connect only with the ipsilateral interneuron in all instars. Afferents from ventral filiform hairs possesses ipsi- and contralateral branches and make monosynaptic connections with both interneurons in first instars. In later instars, the ipsilateral branch, and its synaptic connection to the ipsilateral interneuron, is gradually reduced until it is lost in the adult, whereas the contralateral branch, and its synaptic connection with the contralateral interneuron, is strengthened. Therefore, after an initial overgrowth of fibers and synapses, segregation of fibers occurs involving the loss of synaptic connections. This loss of branches and synapses was prevented by immobilizing a subpopulation of ventral and lateral filiform hairs, or each group independently, so that their normal activity was blocked. In such treated animals afferents from ventral filiform hairs retain their ipsi- and contralateral branches until adulthood. We therefore conclude that afferent activity plays an important role in shaping the final structure and connectivity of afferents, as neither the peripheral position of the receptors nor the hormonal environment was changed by these manipulations.

Afferent Pathways↗

PubMed1994

Convergence of mechanosensory afferents from different classes of exteroceptors onto spiking local interneurons in the locust.

Tactile stimuli to a leg of a locust are detected by two classes of exteroceptors: trichoid sensilla (tactile hairs), which are purely mechanoreceptors, and basiconic sensilla, which serve a dual role as mechano- and chemoreceptors. The trichoid sensilla have the longer shafts, but because the two types of receptors are intermingled over the surface of a leg, both can be excited when the leg contacts an obstacle. This article analyzes the mechanisms by which the tactile sensory information from these two classes of receptor is collated in the CNS so that spatial information is preserved. The mechanosensory afferents from both types of receptors on a hind leg make convergent connections that are excitatory and apparently direct with the same spiking local interneurons in a midline population of the metathoracic ganglion. The anatomy of the afferent projections suggests that the synapses from the two types of receptor are made onto the same region of branches of an interneuron. The slower conduction velocity of the spikes of the basiconic afferents compared to that of the trichoid afferents means that a mechanical stimulus to the tibia will first produce a depolarization caused by the trichoid afferents, followed up to 20 msec later by a depolarization caused by the basiconic sensilla. Each interneuron is excited by a contiguous and overlapping array of trichoid and basiconic receptors that form its receptive field. Different interneurons have different receptive fields such that the surface of the leg is mapped as a series of overlapping receptive fields. Within a receptive field the contribution of individual receptors can be markedly different: some basiconic receptors evoke large-amplitude EPSPs so that each afferent spike can cause a spike in the interneuron, whereas others generate small EPSPs that must sum with other inputs to evoke a spike. The amplitudes of the EPSPs generated by different receptors within a receptive field form gradients that are distributed according to the axes of the leg. The most effective basiconic and the most effective trichoid sensilla within a particular receptive field can be at the same or at different locations on the leg. Tactile sensory information from different types of receptor on one region of a leg is therefore collated initially by particular spiking local interneurons. This organization ensures summation between the inputs from the different types of receptors and should enhance sensitivity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1994

A presynaptic gain control mechanism among sensory neurons of a locust leg proprioceptor.

The chordotonal organ at the femorotibial joint of a locust hind leg monitors extension and flexion movements of the tibia. During evoked or imposed movements of this joint the central terminals of afferent neurons from the chordotonal organ receive depolarizing, inhibitory synaptic inputs. The afferent spikes are therefore superimposed on these depolarizing IPSPs, which are generated indirectly by other afferents from the same organ that respond to the same movement. Each afferent spikes preferentially to particular features of a joint movement, and its synaptic input is typically greatest at the joint position or during the movement that generates its best response. Afferents that respond to only one direction of movement receive synaptic inputs either during movements in both directions, or only during movements in their preferred direction. Phasic velocity-sensitive afferents receive either phasic inputs during movements, or tonic inputs at new sustained joint positions, or both. The spikes of tonic position-sensitive afferents are superimposed on synaptic inputs that are dependent on joint position. The synaptic inputs sum but do not themselves evoke antidromic spikes in the afferent terminals. They reduce the amplitude of orthodromic afferent spikes by 12-28%, and this is accompanied by a reduction of up to 50% in the amplitude of monosynaptic EPSPs evoked by an afferent in postsynaptic leg motor neurons. These interactions suggest that a local gain control mechanism operates between the afferents of this proprioceptor. Thus, the effectiveness of the output synapses of an individual afferent is regulated by the network action of other chordotonal afferents that respond to the same movement.

Action Potentials↗

PubMed1993

Distribution of acetylcholine receptors in the central nervous system of adult locusts.

A polyclonal antibody raised against nicotinic acetylcholine receptor protein from purified locust neuronal membrane was used to analyse the distribution of antigenic sites within the central nervous system of adult Schistocerca gregaria. Light microscopic examination showed that all principal neuropiles in the thoracic ganglia label with the antibody but that the major tracts and commissures do not. Analysis of this pattern of staining in the electron microscope reveals that the receptor is present on specific synaptic and extrajunctional neuronal membranes in the neuropile. Antigenic sites are also evident on the plasma membranes and within the cytoplasm adjacent to Golgi complexes of some neuronal somata, suggesting that these neurones synthesise nicotinic acetylcholine receptors. In addition to neuronal labelling, there is evidence that the receptor is also present on the membranes of three types of glial cells. The implications of this pattern of receptor distribution are discussed.

Animals↗

PubMed1993

Correlation between the receptive fields of locust interneurons, their dendritic morphology, and the central projections of mechanosensory neurons.

The relationships between the morphology and receptive fields of local and intersegmental interneurons that process mechanosensory information from a hindleg of the locust have been analysed. Sensory neurons from tactile hairs project to ventral areas of neuropil in the metathoracic ganglion where they form a 3-dimensional somatotopic map of a hindleg. By contrast, sensory neurons from a proprioceptor at the femoro-tibial joint (the femoral chordotonal organ) project to lateral and more intermediate areas of neuropil and have no branches in the most ventral regions of neuropil. Particular local and intersegmental interneurons respond to stimulation of specific arrays of hairs on a hindleg, or to movements of particular joints. Their receptive fields are defined, in part, by the patterns of excitatory, monosynaptic connections made by these afferents. Each interneuron has a characteristic receptive field and a characteristic morphology defined by its array of branches in the regions of neuropil containing the projections of the afferents that provide its monosynaptic inputs. Interneurons with inputs exclusively from tactile hairs have branches in the most ventral regions of neuropil, while those with exclusively proprioceptive inputs have branches only in more intermediate levels of neuropil. Interneurons with extensive receptive fields from tactile hairs also have extensive areas of branching within the ventral neuropil. Interneurons with receptive fields restricted to particular regions of the leg have branches restricted to the ventral region of neuropil containing the projections of afferents from that part of the leg. Thus, interneurons with inputs only from hairs on the tarsus have branches in the posterior region of neuropil corresponding to the projections of the tarsal afferents, while interneurons with receptive fields on the femur have branches in more anterior regions of neuropil corresponding to the projections of the femoral hair afferents. Interneurons with receptive fields on the tibia have branches in neuropil between the tarsal and femoral projections.

Afferent Pathways↗

PubMed1993

GABA-immunoreactivity in processes presynaptic to the terminals of afferents from a locust leg proprioceptor.

Individually labelled sensory neurons from the femoral chordotonal organ, a proprioceptor at the femoro-tibial joint of a locust hindleg, were analysed by intracellular recording, and by electron microscopical immunocytochemistry to reveal the arrangement of their input and output synapses and to determine whether the input synapses were GABAergic. Intracellular recordings from these sensory neurons show spikes superimposed on a barrage of synaptic potentials during movements of the femoro-tibial joint. These synaptic inputs can be mimicked by GABA. Input synapses are made onto the vesicle-containing terminals of afferents and are often closely associated with the output synapses. By contrast, the axons of the afferents in the neuropil have no vesicles and neither make nor receive synapses. The input synapses to the afferent terminals are made from processes typically a few microns in diameter, whereas the output synapses are made onto much smaller processes of only 0.1-0.2 micron. Input synapses at which an afferent terminal is the only postsynaptic element are common. Where the synapse is dyadic the second postsynaptic element does not usually appear to be a chordotonal afferent. The output synapses from the afferent terminals are usually dyadic. At 78% of the input synapses, the presynaptic neurite showed immunoreactivity to a GABA antibody, supporting the physiological evidence that the presynaptic effects can be mediated by the release of GABA. The remaining (22%) immunonegative synapses are intermingled with those showing GABA immunoreactivity, but their putative transmitter is unknown. These morphological observations suggest that the presynaptic control of the chordotonal afferents is largely mediated by GABAergic neurons, but because other types of neuron also appear to be involved, presynaptic modulation may be more complex than has yet been revealed by the physiology.

Action Potentials↗

PubMed1993

Dynamic cardiomyoplasty in chronic left ventricular failure: an experimental model.

Dynamic cardiomyoplasty continues to attract interest as a therapeutic option in the management of heart failure. In a large animal model of ischemic heart failure, we have compared dynamic cardiomyoplasty with both adynamic cardiomyoplasty and a control group. Heart failure was induced by coronary artery ligation in sheep, and under the same anesthetic dynamic cardiomyoplasty (n = 5), adynamic cardiomyoplasty (n = 4), or no further procedure was performed (n = 5). After recovery the animals were housed for a further 3 months. The dynamic cardiomyoplasty underwent a recognized muscle transformation protocol during this period. At terminal studies, the animals were hemodynamically assessed, both under baseline conditions and after colloid volume loading. The data at baseline were compared with unpaired t tests, and the function curves created by volume loading were compared by analysis of variance. Although the changes at baseline were small, there were highly significant improvements in the function curves in the dynamic cardiomyoplasty group when the stimulators were turned on compared with stimulators off (p = 0.005) for cardiac output; p = 0.035 for left ventricular end-diastolic pressure; p = 0.002 for pulmonary artery capillary wedge pressure; p = 0.004 for stroke volume; and p = 0.003 for cardiac power). There were also significant improvements in indices of cardiac performance when the dynamic cardiomyoplasty group was compared with both the control and adynamic cardiomyoplasty groups. We conclude that there is experimental evidence that cardiomyoplasty augments cardiac function in a model of chronic left ventricular failure.

Animals↗

PubMed1993

Synaptic potentials in the central terminals of locust proprioceptive afferents generated by other afferents from the same sense organ.

Afferent neurons from a proprioceptor [the femoral chordotonal organ (FCO)] at the femoro-tibial joint of a locust hindleg carry patterns of spikes to the CNS in which information is coded about the positions and movements of the tibia. Intracellular recordings from the afferents of this organ as they enter the CNS reveal spikes and depolarizing post-synaptic potentials (PSPs) during voluntary or imposed movements of the joint. Some of these PSPs are generated as a result of spikes in other FCO afferents, and can be evoked experimentally by electrical stimulation of the nerve from the organ. One afferent does not appear to synapse directly on another, but instead activates reliable pathways involving other central neurons. Current clamping of individual afferents in isolated ganglia shows that the PSPs are increased in amplitude by hyperpolarizing currents injected into an afferent, and decreased by depolarizing ones. They reverse at about -68 mV (n = 5). At the normal resting potential of the afferents, -72 mV (+/- 0.42 SE, n = 57), the PSPs are therefore depolarizing, and are associated with an increased conductance of the membrane. The changes in membrane potential and conductances associated with the PSPs can be mimicked by pressure injection of GABA into the regions of neuropil that contain the terminals of the afferents. The potential evoked by GABA is associated with an increased conductance of the membrane and reverses at the same potential as the PSPs. GABA also reduces the PSPs evoked in the terminals, either by movements of the FCO or by electrical stimulation of its nerve. The PSPs and the effects of the GABA-evoked potentials are mimicked by the GABA agonist muscimol. The PSPs are blocked reversibly by picrotoxin. The PSPs and the GABA-evoked potentials both alter the excitability of an afferent terminal by reducing the ability of the membrane to support an action potential. It is suggested that the PSPs are depolarizing, inhibitory potentials generated in the terminals of the afferents by central neurons that release GABA, and that their role is to change the efficacy of the afferent spikes at their first output synapses in the CNS. These interactions could form a graded, gain control mechanism for synaptic transmission at the afferent output synapses that is directly dependent on the features of the mechanical movements of the joint.

Action Potentials↗

PubMed1992

Output connections of a wind sensitive interneurone with motor neurones innervating flight steering muscles in the locust.

The output connections of a bilaterally symmetrical pair of wind-sensitive interneurones (called A4I1) were determined in a non-flying locust (Schistocerca gregaria). Direct inputs from sensory neurones of specific prosternal and head hairs initiate spikes in these interneurones in the prothoracic ganglion. The interneurone with its axon in the right connective makes direct, excitatory connections with the two mesothoracic motor neurones innervating the pleuroaxillary (pleuroalar, M85) muscle of the right forewing, but not with the comparable motor neurones of the left forewing. The connections can evoke motor spikes. The interneurones also exert a powerful, but indirect effect on the homologous metathoracic pleuroaxillary motor neurones (muscle 114), and a weaker, indirect effect on subalar motor neurones of the hindwings. No connections or effects were found with other flight motor neurones, or motor neurones innervating hindleg muscles, including common inhibitor 1 which also innervates the pleuroaxillary muscle. One thoracic interneurone with its cell body in the right half of the mesothoracic ganglion and with its axon projecting ipsilaterally to the metathoracic ganglion receives a direct input from the right A4I1 interneurone. These restricted output connections suggest a role for the A4I1 interneurones in flight steering.

Animals↗

PubMed1992

Local circuits for the control of leg movements in an insect.

To produce behaviour that is adaptive, local circuits in the CNS must transform mechanosensory signals from receptors on the body into changes in movement. Substantial insights into the mechanisms underlying these transformations can be obtained by analysing the local circuits of animals from which intracellular recordings can be made from identified neurones during behavior, thus allowing the complete pathways between inputs and outputs to be followed. In the locust (Schistocerca gregaria) these circuits contain both non-spiking and spiking local neurones so that it is possible to elucidate two basic issues of neuronal integration: (1) the operation of the reflex circuitry that must adjust locomotion, and (2) the integrative role of local circuits that use graded interactions in complex neuropil, perhaps even involving compartmentalized neurones.

Animals↗

PubMed1992

Reliability and effectiveness of transmission from exteroceptive sensory neurons to spiking local interneurons in the locust.

Mechanosensory information from exteroceptive hairs on the legs of a locust is first processed in a segmental ganglion by a midline population of spiking local interneurons for use in adjustments of posture and locomotion. Each interneuron receives excitatory inputs from a characteristic array of these receptors so that the surface of a leg is mapped onto the whole population of interneurons as a series of overlapping receptive fields. The properties of this first synaptic connection, and the contributions of individual afferents forming the receptive fields of the interneurons are examined. The gain of the excitatory synaptic connection between the hair afferents and the interneurons is often high, so that a single afferent spike can lead directly to a spike in the interneuron. Repetitive spikes in a hair afferent evoke EPSPs in an interneuron that decline in amplitude but that may summate. The first EPSP in any sequence is always the largest. The high frequencies of afferent spikes that are evoked by a normal deflection of a hair saturate the synaptic connection so that the amplitude of depolarization is no greater than to a single spike. The EPSPs from two hairs in a receptive field can summate but lead to no heterosynaptic facilitation. High-frequency bursts of spikes in one afferent can reduce the postsynaptic effect of another afferent. The amplitude of the EPSPs and the gain of the synaptic connections differ markedly between the hairs that comprise the receptive field of an interneuron. There are gradients of effectiveness, generally according to the axes of the leg, with one group of adjacent hairs producing the largest-amplitude EPSPs and having the highest gains. Individual hairs may contribute to the receptive field of more than one interneuron, and the gain of these connections may differ. The complexity of a receptive field is further accentuated by the specificity of connections made by the different physiological types of hair receptors. High-threshold hairs may make synaptic connections with an interneuron, but adjacent low-threshold hairs may not. This organization of the receptive fields means that the interneurons are sensitive to certain inputs and can reliably pass on a signal from one hair. It also implies that greater weighting is given to inputs from certain regions.

Animals↗

PubMed1991

Pharmacokinetics and fate of 3H-trospectomycin sulphate, a novel aminocyclitol antibiotic, in male and female rats.

1. The pharmacokinetics and fate of 3H-trospectomycin sulphate, a novel aminocyclitol antibiotic, were examined in male and female rats after intramuscular (i.m.), intravenous (i.v.) and subcutaneous (s.c.) dosing. 2. Total radioactivity levels in plasma were associated with unchanged trospectomycin. Two radioactive components were found in urine, one was indistinguishable from trospectomycin and the other was probably a degradation product formed after excretion or during storage rather than a metabolite. 3. The disappearance of drug from plasma followed a biphasic pattern with half lives of 0.3-0.4 h and 45-80 h and a large distribution volume, which indicated some retention of drug by tissues. Clearance rates were within the normal range for glomerular filtration rate, which indicated that the primary process of elimination is filtration of unchanged drug. 4. Excretion was initially rapid (greater than 40% by 4 h) and mainly into urine (faecal excretion greater than 20%). Urinary excretion was significantly larger in males than females but faecal excretion was significantly smaller, so that there was no significant difference in total excretion. 5. The bioavailability following s.c. dosing was only approximately 75% but there were few other biologically significant differences between the routes of administration. Absorption following i.m. and s.c. dosing was rapid. 6. Clearance rate and volume of distribution were higher in males than females. Over the dose range 50-200 mg/kg the pharmacokinetics appeared to be mostly linear.

Animals↗