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PubMed2000

Masculine copulatory behavior is facilitated by intrathecally administered muscarine.

Behavioral experiments were conducted to examine the role of the cholinergic receptor-agonist muscarine or its antagonist homatropine on the mating behavior of sexually experienced male rats. Male copulatory behavior was recorded after intrathecally administered saline, muscarine (7.5 microg), or homatropine (25 microg). Changes in copulatory behavior were assessed by the following parameters: intromission latency, intromission frequency, intercopulatory interval, ejaculation latency, and postejaculatory interval. Intromission frequency, intercopulatory interval, and ejaculation latency were decreased significantly by muscarine. Intrathecal homatropine decreased the number of copulating animals (five out of 13). In the five animals that were able to ejaculate after homatropine, intromission latency, intercopulatory interval, and ejaculation latency increased significantly. The effects of both drugs on locomotion were also tested. Muscarine induced no significant changes in locomotion compared with saline. A significant increase in locomotion was found after homatropine treatment. These results suggest that acetylcholine, acting at spinal-cord muscarinic receptors, may be involved in ejaculation.

Animals↗

PubMed1984

Influence of antimuscarinics on alpha-adrenoceptors in the female rabbit urethra.

The effects of the tertiary amine atropine and its structural analogues homatropine and scopolamine, as well as the quarternary amine emeprone, were evaluated on noradrenaline (NA)-induced contractions of isolated female rabbit urethral ring preparations. In addition, the abilities of these antimuscarinics to inhibit 3H-dihydro-alpha-ergocryptine (3H-DHE) binding to alpha-adrenoceptors were studied on a crude membrane preparation from the female rabbit bladder base and urethra. Atropine and homatropine depressed the NA-induced contractions in a concentration-dependent way, whereas this was not seen with scopolamine. Emeprone 10(-5) and 10(-4) M augmented the contractions, an effect possibly attributable to a NA-uptake blocking effect. All antimuscarinics displaced specific 3H-DHE binding, the order of potency being atropine greater than homatropine greater than emeprone greater than scopolamine. In general a good correlation was seen between the binding and mechanical activity studies for atropine, homatropine and scopolamine, while this was not found for emeprone. It is concluded that alpha-adrenoceptor blockade by atropine can be observed at concentrations exceeding 10(-7) M. Scopolamine, showing alpha-adrenoceptor blocking properties only in high concentrations, may be used as an alternative for blockade of muscarinic cholinoceptors.

Adrenergic alpha-Antagonists↗

PubMed1989

Atropine- and scopolamine-resistant subtypes of muscarinic receptors in the rabbit aorta.

Tritiated acetylcholine ([3H]ACh) binds specifically to different muscarinic binding sites in the rabbit aorta. The binding of [3H]ACh to endothelial membranes was displacable by nanomolar concentrations of scopolamine but only by micromolar concentrations of atropine and homatropine. The reverse was true for smooth muscle membranes, i.e. [3H]ACh binding was displacable by nanomolar concentrations of atropine and homatropine but only by micromolar concentrations of scopolamine. Pirenzepine, AF-DX 116 and 4-diphenyl-acetoxy-N-methylpiperidine methobromide (4-DAMP) displaced the binding of [3H]ACh from both tissues in the nano- to micromolar range. Our findings indicate that endothelial receptors are characterised by a high affinity for scopolamine, which possesses a scopine base, and that muscle binding sites have a high affinity for antagonists possessing a tropine base (atropine, homatropine). Both the endothelial and smooth muscle binding sites have a low affinity for AF-DX 116, indicating that they are not of the cardiac type.

Animals↗

PubMed2001

Tris(2,2'-bipyridine)ruthenium(II) electrogenerated chemiluminescence of alkaloid type drugs with solid phase extraction sample preparation.

An electrogenerated chemiluminescence (ECL) method for the determination of pethidine, atropine, homatropine and cocaine is described. The optimum conditions were found to be similar for all of these compounds although the ECL emission intensity for cocaine was an order of magnitude lower than for pethidine due to their different chemical structures. Linear calibrations were obtained for all the compounds at pH 10 in borate buffer (0.05 mol l-1) at 1.3 V. Limits of detection of 6.8 x 10(-8), 2.2 x 10(-7), 3.2 x 10(-7) and 6.5 x 10(-7) mol l-1, respectively, were achieved for pethidine, atropine, homatropine and cocaine in standard solutions. Solid-phase extraction was used to separate the drugs from their matrix and the method was applied to the determination of spiked urine samples. The limits of quantitation for pethidine, atropine, homatropine and cocaine in urine were 1.0 x 10(-6), 2.0 x 10(-6), 2.0 x 10(-6) and 4.0 x 10(-6) mol l-1, respectively, with recoveries of between 90 and 110%.

Alkaloids↗

PubMed1999

Ultrasound biomicroscopic study on changes of ocular anterior segment structure after topical application of cycloplegia.

OBJECTIVES: To observe the changes of the ocular anterior segment structure and the relationship between the intraocular pressure (IOP) and these changes after the topical application of cycloplegia using ultrasound biomicroscope (UBM), especially to observe the changes of ciliary body thickness, ciliary process thickness and ciliary process-lens distance. METHODS: The quantitative measurement with UBM and the measurement of IOP were performed before and after the topical application of 2% homatropine solution in 48 normal eyes. The results were statistically analyzed. RESULTS: In the parameters showing the changes of the anterior chamber angle after topical use of 2% homatropine solution, both the trabecular iris angle and the angle opening distance 250 decreased. The iris thickness 1 increased. The anterior chamber became deeper and the iris-lens contact distance became shorter. All these differences were statistically significant (P < 0.05). In the parameters showing the changes of ciliary body, the ciliary body thickness and the ciliary process thickness decreased. The scleral ciliary body angle increased. The iris-zonule distance decreased and the ciliary process-lens distance increased. All these differences were statistically significant (P < 0.05). The IOP increased from 17.63 +/- 3.45 mm Hg to 18.23 +/- 3.53 mm Hg after topical use of 2% homatropine solution, but the difference was not statistically significant (P > 0.05). CONCLUSIONS: After the topical use of cycloplegia, the anterior chamber becomes deeper. The anterior chamber angle becomes narrower, and the ciliary body becomes thinner and moves backward and the ciliary process-lens distance increases. By using UBM the structures of the ocular anterior segment in the living state can be observed and measured quantitatively. The ultrasound biomicroscopic imaging has its advantages in the morphological study of the ocular anterior segment.

Adult↗

PubMed1998

[An ultrasound biomicroscopic study on changes of the structure of ocular anterior segment after topical application of cycloplegia].

OBJECTIVE: To observe the changes of ocular anterior segment and the relation between the intraocular pressure (IOP) and these changes after the topical application of cycloplegia using ultrasound biomicroscope (UBM), especially to observe the changes of ciliary body thickness and ciliary body-lens distance. METHODS: The quantitative measurement of UBM and the measurement of IOP had been done in 48 normal eyes before and after the topical use of 2% homatropine solution. The results were statistically analyzed. RESULTS: In the parameter reflecting the change of the anterior chamber angle after using 2% homatropine, the trabecular iris angle decreased, the angle open distance 250 decreased, the iris thickness 1 increased, the anterior chamber became deeper and the iris-lens contact distance became shorter, and all these differences were statistically significant (P < 0.05). In the parameter reflecting the changes of ciliary body, the ciliary body thickness and the ciliary process thickness decreased, the scleral ciliary body angle increased, the iris-zonule distance decreased and the ciliary body-lens distance increased, and all these differences were significant statistically (P < 0.05). The IOP increased from 2.35 +/- 0.46 kPa to 2.43 +/- 0.47 kPa after the topical use of 2% homatropine, but the differences were not statistically significant (P > 0.05). CONCLUSIONS: After the topical application of cycloplegia, the anterior chamber becomes deeper, the anterior chamber angle becomes narrower, the ciliary body becomes thinner and moves backward and the ciliary body-lens distance increases. By using UBM the structure of ocular anterior segment in its moving state can be observed and these structures can be measured quantitatively. The ultrasound biomicroscopic imaging has its advantages in the morphological study of ocular anterior segment.

Adult↗

PubMed1977

A second conponent of atropine mydriasis.

A patient with Waardenburg syndrome had, in addition to the classical findings, a semidilated fixed pupil which did not react to changes of illumination, to convergence, or to pilocarpine of phospholine iodide. However, it responded normally to locally applied drugs acting on the sympathetic system. The pupil dilated after application of atropine, homatropine, or cocaine. The effect of cocaine, but not of atropine and homatropine, was prevented by pretreatment with guanethidine. It is concluded that the mydriasis caused by atropine and homatropine is partly dependent upon a direct action on the radial smooth muscle.

Atropine↗

PubMed1983

Effect of one year clofazimine therapy on autonomic functions in lepromatous leprosy with lepra (ENL) reaction.

Twenty patients of either sex of Lepromatous leprosy with frequent type II (ENL) reactions were selected for the study after exclusion of autonomic disorders. ANS functions were evaluated before and after Clofazimine therapy at an interval of two months for one year. Sweat function test, valsalva manoeuvre, Histamine triple response, cold pressor test and Homatropine instillation were carried out in twenty normal healthy volunteers (controls) and the (ENL) patients. Clofazimine was administered initially 100 mg three times daily for one month and then gradually reduced to a dose of 100 mg biweekly for the last three months. Before the clofazimine therapy, eighteen patients had abnormal sweat functions, five patients had abnormal valsalva score, five patients had abnormal cold pressor response and all the eighteen patients had abnormal histamine triple response test. Homatropine instillation test was normal in all the patients. ANS functions did not improve significantly with Clofazimine therapy, except in one patients with abnormal cold pressor response who showed slight improvement in pressor response which, however, did not reach the normal value. ANS function tests indicate complete involvement of local axon reflex and hyporeactivity of sympathetic system and cardiac regulatory mechanisms in these patients. Parasympathetic system seems to be normal as seen from Homatropine instillation test.

Autonomic Nervous System↗

PubMed1983

Effect of urea on the activity of certain ophthalmic drugs in man.

The role displayed by urea (2-10%) solutions, on the miotic and mydriatic activities of pilocarpine hydrochloride and homatropine hydrobromide respectively, was investigated on the human eye. At different concentrations, urea exerts no effect on the miotic activity of pilocarpine, whereas in the case of homatropine a negative effect is experienced. For the parameters, area under pupil diameter--time curve (AUC) and maximum pupillary response (MPR), a linear relationship exists between response to homatropine and urea concentration. However, the dependency is more pronounced in conjunction with the MPR parameter.

Drug Interactions↗

PubMed1996

Significance of mobile phase composition in enantioseparation of chiral drugs by HPLC on a cellulose-based chiral stationary phase.

Eight randomly selected pharmaceuticals, which included ibuprofen, ketoprofen, albuterol, acebutolol, propafenone, betaxolol, methylphenidate, and homatropine, were directly separated on a cellulose tris(4-methylbenzoate) chiral stationary phase (CSP) without derivatization via normal phase mode HPLC. Enantioresolution was achieved by the optimization of the type and the ratio of mobile phase modifiers and additives. The modifiers included alcohols; the mobile phase additives were trifluoroacetic acid (TFA) and triethylamine (TEA). It was found that methanol and ethanol were superior to isopropanol as mobile phase modifiers for enhancing chiral separation of some of the chiral drugs. The results also demonstrated that TFA has a dominant effect on chiral separations for both acidic and basic chiral drugs, although for some basic drug such as homatropine, TEA was more beneficial at improving enantioseparation. The separation of acebutolol enantiomers was achieved for the first time by adding both TFA and TEA to the mobile phase. The purpose of this paper is to demonstrate that the applicability of cellulose based CSPs can be expanded by controlling the mobile phase compositions through the addition of trace amounts of achiral additives and the selection of the appropriate alcoholic modifier.

Chromatography, High Pressure Liquid↗

PubMed1999

Enantioseparation of tropa alkaloids by means of anionic cyclodextrin-modified capillary electrophoresis.

Anionic cyclodextrins (CDs), i.e., sulfated CD, sulfobutylether beta-CD (SBE-beta-CD) and heptakis(2,3-di-O-acetyl-6-sulfato)-beta-CD (HDAS-beta-CD), were used to separate the isomers of atropine, homatropine, ipratropium, scopolamine and butylscopolamine. Variations in the pH value and the concentration of the various CDs revealed the sulfated beta-CD to be superior to the other derivatives. In a basic medium at low concentrations of sulfated CD the enantiomers of atropine, homatropine and ipratropium were well resolved in a short migration time, which is appropriate for the routine analysis of the enantiomeric excess. Scopolamine and butylscopolamine compounds could not be separated with either CD.

Anions↗

PubMed1986

The cardio-selectivity of himbacine: a muscarine receptor antagonist.

The antimuscarinic actions of himbacine were compared with those of atropine and/or homatropine on atria, ileum and trachea from guinea-pigs and rat uterus preparations. The antagonism of acetylcholine or carbachol by all the antagonists was competitive on the preparations studied. The pA2 values of himbacine in all smooth muscle preparations were similar (around 7.2) whereas in atria it exhibited about 10-fold higher affinity (pA2 = 8.2). In contrast, both atropine and homatropine had similar affinities for muscarine receptors (pA2 values around 9.1 and 7.2 respectively) in both atria and smooth muscle. It may be concluded from these results that cardiac and smooth muscle muscarine receptors are not homogeneous and that himbacine is a relatively potent and selective antagonist for cardiac receptors. The cardio-selectivity of himbacine supports the concept of heterogeneity of muscarine receptors.

Alkaloids↗

PubMed1978

Effect of variations in temperature on antimuscarinic activity in guinea-pig atria.

The characteristics of the antimuscarinic activity of homatropine, gallamine and stercuronium in guinea-pig atria remained constant over the temperature range 22--37 degrees C in that a linear Arunlakshana-Schild plot was obtained with homatropine and nonlinear plots occurred with gallamine or stercuronium. A trend towards higher dose-ratios with reduction in temperature was only significant for gallamine.

Alkaloids↗

PubMedDate not supplied

Antimuscarinic action of an alkane-bis-ammonium compound alone and in combination with (+)-benzetimide.

Heptane-1,7-bis-(dimethyl-3'-phthalimidopropylammonium bromide) ('C7/3-phthalimido-propyl') in concentrations of 10(-7) to 0.5 X 10(-3) inhibited negative inotropic responses to carbachol or acetylcholine to a similar extent in the electrically stimulated isolated guinea-pig left atrium. However, the degree of antagonism of responses to carbachol was less than expected for a competitive antagonist when the higher concentrations of 'C7/3-phthalimido-propyl' were employed. When 'C7/3-phthalimido-propyl' was combined with competitive antagonists such as (+)-benzetimide, atropine or homatropine the degree of antagonism was greater than expected for combination of 2 competitive antagonists. Qualitatively similar results were obtained in the presence of practolol (1.5 X 10(-5) M). The results obtained with 'C7/3-phthalimido-propyl' are shown to agree with theoretical predictions for a metaffinoid antagonist which influences the affinities of both agonists and competitive antagonists by combining with a regulatory site distinct from, but interdependent with the binding sites for agonists and competitive antagonists. Further, it is shown that the alkane-bis-ammonium compound produces a much greater reduction in the affinity of carbachol than that of the competitive antagonists and as a consequence causes 'supra-additive' effects when combined with a competitive antagonist. The reduction in the affinity of (+)-benzetimide produced by 'C7/3-phthalimido-propyl' did not differ significantly from the reduction in the affinities of atropine or homatropine.

Acetylcholine↗

PubMed1991

In vivo pupillary constrictor effects of substance P in man.

The ocular effects of substance P (SP) were studied in 13 normal volunteers. Various concentrations of SP (0.135, 1.35 and 135 micrograms per 100 microliters) were instilled into the conjunctival sac and pupillary area changes were evaluated by means of an electronic pupillometer. The ability of SP to modify the mydriasis induced by pretreatment with 1% homatropine eyedrops was also studied. The instillation of SP produced miosis in a dose-dependent manner without provoking any ocular disturbances. Furthermore, the highest concentration tested was unable to reduce the homatropine-induced mydriasis. These findings indicate that SP exerts a pupillokinetic action in humans which probably occurs via a receptor mechanism. Since muscarinic blockade is not overcome by the peptide instillation, the results do not clarify whether SP causes miosis acting on iris muscles and/or cholinergic fibres.

Adult↗

PubMed1986

Comparative behavioral effects of anticholinergic agents in cats: psychomotor stimulation and aggression.

The effect on behavior of eight anticholinergic agents: atropine, scopolamine, trihexyphenidyl, biperiden, homatropine, eucatropine, hexocyclium and propantheline, injected into the cerebral ventricle (ICV) of the cat was investigated and compared. The anticholinergic agents evoked: (1) psychomotor stimulation such as miaowing, loud calling, restlessness, impelling locomotion, jumping, vacant staring, apprehension and loss of interest of the surroundings; (2) aggression, hissing, threat, attack, defense, fighting with paws and flight; (3) autonomic responses including mydriasis, tachypnea, dyspnea, licking, vomiting, salivation, micturition and defection; and (4) motor phenomena comprising scratching, ataxia, rigidity, tremor, weakness with adynamia or myoclonic jerks. Convulsions appeared only after ICV injections of atropine and homatropine. The most characteristic behavioral effect of anticholinergic agents was psychomotor stimulation accompanied by mild aggressive responses. The only exception was propantheline which caused a muscular weakness and adynamia. Atropine and scopolamine alone induced a dose-dependent impelling locomotion as well as fighting behavior. Carbachol and eserine injected intracerebroventricularly reversed the locomotion autonomic and motor phenomena produced by anticholinergic agents administered similarly. It is suggested that anticholinergic agents acting as partial agonists, can produce their behavioral effects through central cholinoceptive sites.

Aggression↗

PubMed2006

Increasing the scale of true moving bed electrophoretic separations using filtration to reduce solvent volumetric flows between sections II and III.

Over the past decade the moving bed process has become a commonly used tool for the continuous separation of chiral compounds, and its recent application to electrophoretic separations allows the technique to be used as a model system for moving bed method improvements. Much of the recent research on moving bed separations has focused on improving the technique's efficiency and increasing the maximum attainable throughput. This paper presents a novel method for reducing or reversing the increases in tailing that stem from the addition of the feed stream in a moving bed process by adding a filtration unit which retains the products while removing fluid from the boundary between the sections above and below the feed stream. This filtration-enhanced moving bed process was applied to a true moving bed (TMB) electrophoresis separation in the Vortex Stabilized Electrophoresis Apparatus, and its effect on a homatropine enantiomer separation was studied. Experiments showed that there is a 2.4-fold increase in the homatropine processing rate when 0.5 ml/h of water is removed through a reverse osmosis filter at the boundary between the sections above and below the feed stream. In order to further understand the process, filtration-enhanced TMB (FE-TMB) was also analyzed using a linear model of the system which shows that the 99% purity operating region of the separation is greatly increased even with moderate permeate flowrates.

Adsorption↗

PubMed2006

Role of the medial prefrontal cortex in cardiovascular responses to acute restraint in rats.

The medial prefrontal cortex (mPFC) modulates neurovegetative and behavioral responses, being involved in memory, attention, motivational and executive processes. There is evidence indicating that mPFC modulates cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint is an unavoidable stress situation that evokes marked and sustained cardiovascular changes, characterized by elevated blood pressure (BP) and intense heart rate (HR) increase. We presently report effects of mPFC pharmacological manipulations on BP and HR responses evoked by acute restraint in rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl2 (1 mM) in the mPFC prelimbic area (PL) increased HR response to acute restraint, without significant effect on the BP response. This result indicates that PL synaptic mechanisms have an inhibitory influence on restraint-evoked HR changes. Injections of the non-selective glutamatergic receptor antagonist kynurenic acid (0.02 M) or the selective N-methyl-d-aspartic acid (NMDA) receptor glutamatergic antagonist (LY235959) (0.02 M) caused effects similar to cobalt, suggesting that local glutamatergic neurotransmission and NMDA receptors mediate the PL inhibitory influence on restraint-related HR responses. Pretreatment with the non-non-N-methyl-D-aspartic acid glutamatergic antagonist glutamatergic antagonist glutamatergic receptor antagonist NBQX (0.02 M) did not affect restraint-related cardiovascular responses, reinforcing the idea that NMDA receptors mediate PL-related inhibitory influence. Pretreatment with the glutamatergic-receptor antagonists did not affect baseline BP or HR values. I.v. pretreatment with the quaternary ammonium anticholinergic drug homatropine methyl bromide (0.2 mg/kg) also increased the restraint-related HR response to values similar to those observed after treatment with kynurenic acid or LY235959, thus, suggesting that PL inhibitory influence on restraint-evoked heart rate increase could be related to increased parasympathetic activity. This dose of homatropine had no significant effects on baseline BP or HR values. Results suggest a PL inhibitory influence on restraint-evoked HR increase. They also indicate that local NMDA receptors involved in parasympathetic activation mediate PL inhibitory influence on restraint-evoked HR increase.

Analysis of Variance↗