“Sudden Drop” in Blood Pressure is Associated With Recanalization After Thrombolysis

We aim to investigate whether the phenomenon of “sudden drop” in blood pressure (BP) within the first 2 hours is associated with vessel recanalization.We retrospectively examined clinical and imaging data from a consecutive series of patients with stroke with large vessel occlusion treated with intravenous thrombolysis (IVT). BP was monitored every 15 minutes during the first 2 hours, then every 30 minutes for 6 hours, and then every hour for 16 hours.We observed the phenomenon of “sudden drop” in systolic BP (≥20 mm Hg) in 82 (50.9%) patients in the first 2 hours and vessel recanalization in 87 (54.0%) patients 24 hours after treatment. This phenomenon was independently associated with recanalization (odds ratio 2.100; 95% confidence interval: 1.085–4.062; P = 0.028) after adjusting for the history of atrial fibrillation, coronary heart disease, and hypertension.The phenomenon of “sudden drop” in systolic BP with 20 mm Hg or greater between 2 continuous measurements within the first 2 hours is associated with recanalization after IVT in patients with large vessel occlusion, especially for middle cerebral artery occlusion.     

Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.

In order to develop a better dopamine receptor radioligand, [3H[apomorphine was prepared and tested for dopamine-like binding properties in both calf and human brain tissues. Specific binding of [3H]apomorphine was defined as that binding which occurred in the presence of 1 muM (-)-butaclamol (an inactive neuroleptic) minus that occurring in the presence of 1 muM (+)-butaclamol (active neuroleptic). The specific binding was saturable, the number of sites being double that of specific [3H]dopamine binding, and occurred primarily in dopamine-rich regions of postmortem human brains. The binding had a dissociation constant of 0.9 nM for human caudate (2 nM for calf caudate) and was blocked by dopamine and norepinephrine, but not by isoproterenol or (-)-propranolol, distinguishing it from a beta-adrenergic receptor. Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor.     

Pseudo and resistant hypertension: A chaotic perspective

Systemic blood pressure (BP) may oscillate for homeostatic needs (equilibrium by constancy) or just as shifts in other intrinsic and extrinsic variables known as allostatic changes. This transitory pressure often rises alerts physicians to out‐of‐control hypertension or even hypertensive crisis. There is a very complex theory underlying these stochastic phenomena, which physicists and mathematicians translate into a single word: chaos. These changes happen according to a stochastic probabilistic pattern that presumes chaotic but somewhat predictable and nonlinear modeling of BP‐related dynamics as a mathematical approach. Based on the chaos theory, small changes at the initial BP (baseline overtime) values could disturb the homeostasis leading to extreme BP chaotic shifts. These almost insignificant oscillations may also affect other variables and systems, leading to the misdiagnosis of hypertension, “out‐of‐control” BP levels, and resistant hypertension (RHT). Thus, these unpredictable and transient increases in BP values may be improperly diagnosed as the white coat and masked or resistant hypertension. Indeed, the interference of the chaos in any phenotype of (true or false) hard to control BP is not considered in clinical settings. This review provides some basic concepts on chaos theory and BP regulation. Besides pseudoresistant hypertension (lack of adherence, circadian variations, and others (white‐coat, masked, early morning effects or hypertension), chaotic changes can be responsible for out‐of‐control hypertension.     

Experimental and Clinical Approaches to Treatment of Hypertension by Dopamine Receptor Agonists

The action of several dopamine agonists on blood pressure was investigated. In dogs, apomorphine induced a decrease in blood pressure and an increase in heart rate. These effects were suppressed by intravenous haloperidol or phentolamine. Intravenous but not intracisternal domperidone suppressed the hypotensive responses elicited by intravenous or intracisternal apomorphine. Furthermore, the hypotensive effect of bromocriptine or apomorphine was abolished in adrenal demedullated dogs. Apomorphine and bromocriptine decreased adrenal catecholamine levels. In men, the acute hypotensive property of apomorphine (but not the long term effect of bromocriptine) was suppressed by pretreatment with domperidone. In hypertensive Parkinsonians, bromocriptine reduced blood pressure, induced an increase in inulin clearance, a decrease in plasma creatinine concentration and in renal vascular resistances. These results suggest that dopamine agonists (like apomorphine or bromocriptine) reduce blood pressure through both a decrease in sympathetic tone and an improvement in renal function. However, the mechanism of the acute and long term hypotensive effects could be different only involving peripheral mechanisms after acute     

Utility of tolcapone in fluctuating Parkinson’s disease

Fluctuating Parkinson’s disease (PD) represents a clinical management challenge. The primary utility of levodopa in patients with PD is moderated by the “wearing off” phenomena seen with long-term use. COMT inhibitors slow down the rapid metabolism of levodopa, resulting in a more-sustained response to dopaminergic therapy. Tolcapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor, shown to have both peripheral and central effects. In clinical trials, tolcapone has been shown to reduce “off” time, increase “on” time, improve patient and clinician assessments of disease severity, and improve patient quality of life. In a SWITCH study, tolcapone was associated with greater duration of “on” time than remaining on entacapone. Adverse effects of tolcapone are related to the class, with the exception of rare cases of hepatotoxicity. Tolcapone has been recently reintroduced on the European market and recent guidance from the US Food and Drug Administration has reduced the hepatic monitoring requirements for patients initiating tolcapone therapy. With proper monitoring, tolcapone is an effective, well-tolerated drug useful in the management of patients with fluctuating PD.     

Dopaminergic regulation of pituitary gonadotrophin-releasing hormone receptor activity in the goldfish (Carassius auratus)

In goldfish, dopamine acts as an endogenous inhibitor of basal and gonadotrophin-releasing hormone (GnRH)-stimulated gonadotrophin release. The purpose of the present study was to investigate the effects of dopamine on the pituitary GnRH receptors in vivo and in vitro in goldfish. The goldfish pituitary contains two classes of GnRH-binding sites, a high-affinity/low-capacity site and low-affinity/high-capacity site. Injection of domperidone, a dopamine antagonist, resulted in a dose- and time-related increase in capacity of both the high- and low-affinity GnRH-binding sites; apomorphine, a dopamine agonist, completely reversed this effect. The effects on GnRH receptor capacity correlated very closely with changes in serum gonadotrophin concentrations. Domperidone was generally without effect on GnRH-binding affinity; however, a small but significant decrease in affinity was observed for the low-affinity binding site at 18 h after injection of the highest dose of domperidone used (40 mumol/kg body weight). Treatment with apomorphine of goldfish pituitary fragments in a perifusion system caused a decrease in the capacity of both the high- and low-affinity GnRH-binding sites without affecting binding affinity; domperidone reversed this effect. It is concluded that the dopaminergic inhibition of basal and GnRH-stimulated gonadotrophin release in goldfish might, in part, be the result of a down-regulation of the pituitary GnRH receptors; this effect of dopamine can be achieved by a direct action at the pituitary level.     

Methotrexate can prevent cardiovascular events in patients with rheumatoid arthritis: An updated meta-analysis

Aims:The incidence of cardiovascular events (CVEs) in patients with rheumatoid arthritis (RA) is higher than that in people without RA. This may be because inflammation promotes the progression of atherosclerosis. Anti-inflammatory drugs might reduce the occurrence of CVEs in patients with RA. Methotrexate (MTX) is a conventional synthetic anti-rheumatic drug that is widely used in the treatment of RA. We performed a meta-analysis to determine whether MTX can prevent CVEs in RA patients. Then, we discussed the possibility of using MTX to prevent recurred CVEs in patients with coronary heart disease (CHD).Methods:We searched PubMed, Embase, Web of Science, and the Cochrane Library using the key words “methotrexate,” “cardiovascular,” “acute coronary syndrome,” “coronary heart disease,” “myocardial infarction,” “angina pectoris,” and “rheumatoid arthritis.” The efficacy outcome was defined as a composite of CVEs, including stable angina, acute coronary syndrome, stroke, heart failure, and cardiac death.Results:A total of 10 studies and 195,416 RA patients were included in our meta-analysis, and the effect size of relative risk (RR) was pooled using a fixed effect model. The results showed that MTX prevented CVEs in RA patients (RR: 0.798, 95% CI 0.726–0.876, P = .001, I² = 27. 9%).Conclusion:MTX can prevent CVEs in RA patients, but there is not sufficient evidence for using MTX to treat patients with CHD.     

Pre-operative nutrition assessments do not improve outcomes in cerebral palsy patients undergoing varus derotational osteotomy

Pre-operative nutritional assessments have been used as a “cornerstone” to help optimize nutritional status and weight in children with cerebral palsy (CP) to lower the risk of postoperative complications. However, the potential value of nutritional assessments on surgical outcomes in patients with CP undergoing major orthopedic surgery remains unproven.Do pre-operative nutritional assessments reduce complication rates of varus derotational osteotomy surgery in children with CP? Are complication rates higher in patients with a gastrostomy tube (G-tube) and can they be decreased by pre-operative nutritional assessment?One-hundred fifty-five patients with CP who underwent varus derotational osteotomy from January 1, 2012 through December 31, 2017 at a tertiary pediatric hospital with minimum 6 months follow-up were retrospectively identified. One-hundred-ten (71%) were categorized as “non-ambulatory” (Gross Motor Function Classification System [GMFCS] IV–V), and 45 (29%) as “ambulatory” (GMFCS I–III). Variables assessed included age, GMFCS level, G-tube, body mass index (BMI) percentile, complications, and if patients underwent pre-operative nutritional assessment.One-hundred-eleven patients (71.6%) underwent pre-operative nutritional assessment. Sixty-two of 155 patients (40.0%) had G-tubes. In non-ambulatory patients with G-tubes, BMI percentile changes were not significantly different between patients with a pre-operative nutritional assessment compared to those without at 1 (P = .58), 3 (P = .61), 6 (P = .28), and 12 months (P = .21) postoperatively. In non-ambulatory patients who underwent pre-operative nutritional assessment, BMI percentile changes were not significantly different between those with and without G-tubes at 1 (P = .61), 3 (P = .71), 6 (P = .19), and 12 months (P = .10). Pulmonary complication rates were significantly higher in non-ambulatory patients with G-tubes than in non-ambulatory patients without G-tubes (20% vs 4%, P = .03). Pre-operative nutritional assessments did not influence postoperative complication rates for non-ambulatory patients with or without a G-tube (P = .12 and P = .16, respectively). No differences were found in postoperative complications between ambulatory patients with and without G-tubes (P = .45) or between ambulatory patients with or without nutritional assessments (P = .99).Nutritional assessments, which may improve long term patient nutrition, should not delay hip surgery in patients with CP and progressive lower extremity deformity. Patients and their families are unlikely to derive any short-term nutritional improvement using routine pre-operative evaluation and surgical outcomes are unlikely to be improved.Level of Evidence: III, retrospective comparative.     

Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis: a single centre Indian experience

BACKGROUND: Fungal peritonitis (FP) is a serious complication in patients on continuous ambulatory peritoneal dialysis (CAPD). We reviewed our FP cases to analyse the causative agents and possible risk factors in relation to FP and its outcome and mortality. METHODS: Records of all FP cases were reviewed. FP was diagnosed based on effluent cell count and positive fungal culture in suitable media. RESULTS: Between October 1993 and November 2001, 261 patients underwent CAPD. FP was detected in 28 patients, one episode in each patient (14.3% of the total peritonitis episodes). Candida species and dematiaceous fungi+/-Candida species were responsible for 89.3 and 10.7% of episodes, respectively. Patients with preceding bacterial peritonitis (BP) developed FP more frequently (25.6%) than de novo cases (2.9%) (P<0.0001) and lower proportion of them continued CAPD (8.6% vs. 60%; P=0.007). Mortality in patients having abdominal pain with and without fever, and catheter in situ was significantly higher than in those patients who did not have these risk factors (9/11 vs. 6/17, P=0.01; 13/17 vs. 2/11, P=0.003; 6/6, vs. 9/22, P=0.01, respectively). CONCLUSIONS: Higher proportion of our patients had FP; preceding BP was a significant risk factor for development of FP and technique failure. Abdominal pain+/-fever in patients and catheter in situ were identified as risk factors associated with mortality.     

The apomorphine test in heroin addicts

Chronic administration of opiates to laboratory animals induces supersensitivity of the dopamine receptors in the cerebral areas innervated by the mesotelencephalic dopamine pathways. In humans, the in vivo study of the sensitivity of the dopamine neurotransmitter system in Parkinson's patients can be done by means of the apomorphine test, which consists of measuring the number of yawns induced by the subcutaneous administration of low doses of apomorphine (0.005 mg/kg). If chronic opiate use in humans, as in experimental animals, results in supersensitivity of the dopamine systems, the apomorphine test could differentiate between heroin addicts and healthy volunteers, with the former showing greater number of yawns. In order to test this hypothesis we carried out the apomorphine lest in two groups of subjects: a group of male heroin addicts attending our Addiction Treatment Centre for detoxification and the other group consisting of healthy volunteer male university students. Results showed that subcutaneous apomorphine administration induced a greater number of yawns (p < 0.05) in the group of heroin addicts as compared with the group of healthy volunteers, suggesting that heroin addicts present an enhanced sensitivity of the dopamine neurotransmitter system.     

Identifying patterns of diurnal blood pressure variation among ELSA‐Brasil participants

Ambulatory blood pressure monitoring (ABPM) is the gold standard method for the diagnosis of hypertension. ABPM provides a set of repeated measurements for blood pressure (BP), usually over 24 h. Traditional approaches characterize diurnal BP variation by single ABPM parameters such as average and standard deviation, regardless of the temporal nature of the data. In this way, information about the pattern of diurnal BP variation and relationship between parameters is lost. The objective of this study was to identify and characterize daily BP patterns considering the set of repeated measures from 24‐h ABPM. A total of 859 adult participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil) performed a 24‐h ABPM record. Hypertension, sex, age, race/color, education, marital status, smoking, alcohol, physical activity, and BMI were the covariables analyzed. Techniques for longitudinal clustering, multinomial models, and models with mixed effects were used. Three daily BP patterns were identified. Daily BP patterns with high BP presented higher standard deviation and morning surge and lower nocturnal dipping. They showed greater systolic BP variability and faster rise than fall in diastolic BP during sleep. Hypertensive, “pardos,” and men had greater odds to present these patterns. Daily BP patterns with high BP presented the worst profile concerning ABPM parameters associated with cardiovascular risk. The daily BP patterns identified contribute to the characterization of diurnal BP variation.     

Correlation between striatal dopamine D2/D3 receptor binding and cardiovascular activity in healthy subjects

BACKGROUND: The relationship between the striatal dopaminergic system and cardiovascular activity is not well known. The aim of this study is to investigate the relationship between striatal D2/D3 receptor binding and cardiovascular activity. METHODS: The striatal D2/D3 receptor binding of 34 healthy volunteers was assessed by the single-photon emission computed tomography (SPECT) imaging method with the [123I]-iodobenzoamide (IBZM) ligand. The ratio of the radioactivity in the striatum (St) and the frontal cortex (Fc) (St/Fc ratio) was used as the marker for striatal D2/D3 receptor binding. Their cardiac autonomic functions were measured by continuously monitoring their heart rate and blood pressure (BP) in supine position during 10 min. The heart rate variability (HRV) was analyzed by spectral analysis and the geometric method. RESULTS: The St/Fc ratio of striatal dopamine D2/D3 receptor binding correlated negatively with heart rate (HR), and positively with cardiac vagal index (CVI) and low frequency (LF) power in healthy subjects who were in a supine resting position. CONCLUSIONS: Striatal dopamine D2/D3 receptors may play a part in cardiovascular regulation.     

In vivo imaging of pituitary tumours using a radiolabelled dopamine D2 receptor radioligand

OBJECTIVE Knowledge of the dopamine D2 receptor status of pituitary tumours may play a predictive role in differential diagnosis and therapeutic decisions. This study was performed to evaluate the value of pituitary dopamine D2 receptor scintigraphy with (S)-2-hydroxy-3-¹²³I-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (¹²³I-IBZM) in the diagnostic evaluation of patients with pituitary tumours. DESIGN AND PATIENTS Scintigraphy using ¹²³I-IBZM was performed in 5 patients with PRL-secreting macroadenomas, 2 patients with PRL-secreting microadenomas, 17 patients with clinically non- functioning pituitary adenomas (NFPAs), 12 patients with GH-secreting adenomas and 1 patient with a TSH-secreting macroadenoma. RESULTS Single-photon emission tomography (SPECT) showed significant uptake of ¹²³I-IBZM in the pituitary region in 3/5 macroprolactinoma patients. These results closely correlated with the response of plasma PRL levels to the dopamine D2 receptor agonist quinagolide. In two scan-positive prolactinoma patients, repeated SPECTs during therapy with quinagolide showed a reduction in the pituitary uptake of ¹²³I-IBZM. Pituitary SPECT was negative in the 2 microprolactinoma patients, who responded to quinagolide administration. In 4/17 patients with NFPA, significant uptake of the radioligand in the pituitary region was observed. In 2/3 scan-positive NFPA patients, who were treated with quinagolide, shrinkage of the pituitary tumours was observed. Treatment with quinagolide resulted in stabilization of tumour growth in the other scan- positive patients. Four out of 17 patients with NFPA and a negative SPECT were treated with quinagolide. Tumour growth was observed in 1 patient, and tumour size did not change in the other 3 patients. The pituitary region of none of the 12 acromegaly patients showed significant uptake of ¹²³I-IBZM. Sensitivity of the GH-secreting adenomas to quinagolide was demonstrated in 8/12 patients in vivo by an acute test, and in 6/9 of the tumours in vitro. Pituitary SPECT was negative in the patient with the TSH-secreting macroadenoma and this tumour also showed no sensitivity to quinagolide in vivo or in vitro. CONCLUSIONS We conclude that ¹²³I-IBZM is a ligand for in vivo imaging of dopamine agonist- sensitive macroprolactinomas, but not for microprolactinomas or GH-secreting adenomas. The technique potentially provides a means of predicting the dopamine agonist-responses of non-functioning pituitary adenomas in vivo.     

Disaster hypertension and cardiovascular events in disaster and COVID‐19 pandemic

The incidence of large disasters has been increasing worldwide. This has led to a growing interest in disaster medicine. In this review, we report current evidence related to disasters and coronavirus disease‐2019 (COVID‐19) pandemic, such as cardiovascular diseases during disasters, management of disaster hypertension, and cardiovascular diseases associated with COVID‐19. This review summarizes the time course and mechanisms of disaster‐related diseases. It also discusses the use of information and communication technology (ICT) as a cardiovascular risk management strategy to prevent cardiovascular events. During the 2011 Great East Japan Earthquake, we used the “Disaster Cardiovascular Prevention” system that was employed for blood pressure (BP) monitoring and risk management using ICT. We introduced an ICT‐based BP monitoring device at evacuation centers and shared patients’ BP values in the database to support BP management by remote monitoring, which led to improved BP control. Effective use of telemedicine using ICT is important for risk management of cardiovascular diseases during disasters and pandemics in the future.     

CT-based attenuation correction versus prone imaging to decrease equivocal interpretations of rest/stress Tc-99m tetrofosmin SPECT MPI.

BACKGROUND: The purpose of this study was to compare stress supine single photon emission computed tomography (SPECT) imaging with attenuation correction (AC) via computed tomography-based attenuation maps with stress prone SPECT imaging with regard to the rate of equivocal interpretation of rest/stress myocardial perfusion imaging. METHODS AND RESULTS: Interpretations for 324 consecutive patients referred for rest/stress myocardial perfusion imaging were performed by use of the following sets of poststress SPECT images: supine with no AC (NC), supine NC/AC, supine NC/prone, and all images. The number of equivocal studies decreased with additional imaging: supine NC, 40%; supine NC/prone, 18%; supine NC/AC, 11%; and all images, 8%. The supine NC/AC sets of images reduced the number of defects to a greater extent than the supine NC/prone images for all patients (P = .01), men (P = .002), and women (P = .425). For the inferior (but not the anterior) wall, the percent decrease in defects with supine NC/AC images was lower as compared with supine NC/prone images. CONCLUSION: Interpretation with all images resulted in the fewest equivocal studies. The supine NC/AC images reduced the number of equivocal studies to a greater extent than the supine NC/prone images. AC and prone imaging were more helpful in men than women and were more helpful to resolve inferior than anterior wall defects. Adding prone imaging to supine imaging without and with AC does not significantly alter the number of equivocal interpretations.     

Dobutamine stress echocardiography versus quantitative technetium-99m sestamibi SPECT for detecting residual stenosis and multivessel disease after myocardial infarction

OBJECTIVE—To compare the relative accuracy of dobutamine stress echocardiography (DSE) and quantitative technetium-99m sestamibi single photon emission computed tomography (mibi SPECT) for detecting infarct related artery stenosis and multivessel disease early after acute myocardial infarction.
DESIGN—Prospective study.
SETTING—University hospital.
METHODS—75 patients underwent simultaneous DSE and mibi SPECT at (mean (SD)) 5 (2) days after a first acute myocardial infarct. Quantitative coronary angiography was performed in all patients after imaging studies.
RESULTS—Significant stenosis (> 50%) of the infarct related artery was detected in 69 patients. Residual ischaemia was identified by DSE in 55 patients and by quantitative mibi SPECT in 49. The sensitivity of DSE and mibi SPECT for detecting significant infarct related artery stenosis was 78% and 70%, respectively, with a specificity of 83% for both tests. The combination of DSE and mibi SPECT did not change the specificity (83%) but increased the sensitivity to 94%. Mibi SPECT was more sensitive than DSE for detecting mild stenosis (73% v 9%; p = 0.008). The sensitivity of DSE for detecting moderate or severe stenosis was greater than mibi SPECT (97% v 74%; p = 0.007). Wall motion abnormalities with DSE and transient perfusion defects with mibi SPECT outside the infarction zone were sensitive (80% v 67%; NS) and highly specific (95% v 93%; NS) for multivessel disease.
CONCLUSIONS—DSE and mibi SPECT have equivalent accuracy for detecting residual infarct related artery stenosis of  50% and multivessel disease early after acute myocardial infarction. DSE is more predictive of moderate or severe infarct related artery stenosis. Combined imaging only improves the detection of mild stenosis.


Keywords: myocardial infarction; dobutamine echocardiography; single photon emission computed tomography; SPECT; myocardial ischaemia     

A formula for quantifying the effects of substrate cycles (futile cycles) on metabolic regulation. Its application to glucose futile cycle in liver as studied by glucose-6-phosphatase/glucokinase determinations

Summary Substrate cycles (SC) are formed by a ‘forward pathway’ (FP) and a ‘backward pathway’ (BP), the difference between FP and BP forming the ‘metabolic flux’ (MF) through the route of which the cycle is part. SC modulate regulatory effects, i.e. amplify or reduce the % change in MF compared to the % change in FP and BP, thus affecting the sensitivity to regulatory factors, including hormones. A formula is given to calculate (with an approximation of ± 0.5) the ‘flux response index’ (FRI), i.e. the factor by which the % change in FP plus the % change in BP must be multiplied to obtain the % change in metabolic flux, when FP and BP undergo opposite, nonunidirectional changes (as is often the case in metabolic regulation). The formula is: FRI = [(FP+BP)/(FP-BP)]/2. By this formula we evaluated the hepatic activities of glucose-6-phosphatase and glucokinase (which roughly reflect hepatic glucose production and uptake, respectively), i.e. the two enzymes that catalyze the cycle between glucose-6-phosphate (glucose-6-P) and glucose. Based on data obtained in normal, nonobese diabetic and obese diabetic subjects as well as in normal, streptozotocin-diabetic, and obese diabetic (ob/ob) mice, we found that FRI was reduced in non-obese diabetic humans and animals whereas it was increased in obese-diabetic humans and mice, compared to normal controls. Thus, diabetes without obesitydecreases, and obesity with diabetesincreases, the sensitivity of the glucose-6-P/glucose cycle to regulatory agents.     

Rapid death during cocaine abuse: a variant of the neuroleptic malignant syndrome?

A mechanism for rapid death in cocaine abusers is proposed based on the neuroleptic malignant syndrome (NMS). The mechanism involves decreased postsynaptic availability of dopamine either through direct receptor blockade, as postulated in classical NMS, or through relative dopamine depletion, as postulated in cocaine withdrawal. The hallmark symptoms of NMS include hyperpyrexia and muscular rigidity, but the cocaine associated syndrome is atypical in having minimal rigidity. This lack of muscle rigidity, however, appears to be consistent with NMS-like syndromes accompanying other conditions involving dopamine depletion rather than blockade. Treatment implications are that dopamine antagonists, which are usually prescribed for cocaine overdose, may be contraindicated and instead, dopamine agonists may reverse this rapidly fatal syndrome.