Overload

Bromocriptine

Category: Medicines

Type

Involuntary and voluntary

Introduction and description

 

Bromocriptine is sold under the trade names Parlodel, Cycloset, and Brotin (Pakistan), it is an ergoline derivative and a pharmaceutical used in the treatment of:


In 2009, bromocriptine mesylate was approved by the FDA for treatment of type 2 diabetes under the trade name Cycloset.

This eclectic mixture of illnesses and diseases means I have had to give it a section on its own.  This is a quote from Wikipedia “It is currently unknown how this drug improves glycemic control

 

The more general side effects it produces are shown below, but it has a very impressive record for producing hallucinations.  To quote the literature:

Bromocriptine use has been anecdotically associated with causing or worsening psychotic symptoms  - its mechanism is in opposition of most antipsychotics, whose mechanisms generally block dopamine.”

This has not gone unnoticed in the so called recreational drug user community.  Bromocriptine directly stimulates Dopamine-2-receptors and it's a LSD-like derivate but is without the effects that LSD has, making it completely ineffective as a recreational drug.  Unfortunately this appears not to be understood by some users.  Being precise, Bromocriptine is a semisynthetic derivative of a natural ergot alkaloid, ergocriptin (a derivative of lysergic acid - LSA), so the link is even weaker than most users seem to think.

This person [from EROWID] used a combination of Bromocriptine, Amantadine [prescribed] and Cannabis.  The next day he realised he had altered his brain.....

 

The horror came when I came to watch the Simpsons. The show wasn't funny at all, it seemed like crap to me. Before that event last night, I was the world's biggest Simpsons fan because the jokes are more intelligent then any other comedy; .... But right now it wasn't funny at all. And because the Simpsons often have some kind of very wicked humour it also in addition seemed like complete crap, absolute nonsense. I was terrified. I turned off the telly and sat down and sat there for a long time, maybe an hour or two doing nothing. I was deeply shocked.
From then on the state didn't change. I don't get the jokes in comedies, in other movies, in the whole TV; in addition in theater, printed jokes and even jokes folks tell me, that is, almost all jokes; .... In the meanwhile I managed it to UNDERSTAND them again (though not always) but they are not funny. I only laugh seldom; and not that I cannot laugh anymore, I simply can't cry. Now and then it occurs that I am crying but VERY VERY rarely, same as laughing.
I don't know what happed that night to my neural structure. .... I have almost completely lost the capability to understand humour.
My life is like horror now; it's like physically losing a part of your body, an arm or somewhat. Social interaction has become very difficult since then. I don't know what exactly was the cause of this brain kill, and in don't think I ever will. The neurochemical interactions are too complex. I don't think it was the weed alone that caused the destruction since I have been smoking weed for years and in far greater amounts than on that evening.

 Remember that apart from the cannabis, these drugs were prescribed to this chap.

Background

If we concentrate on the hallucinations first, taking a snapshot in time and using the figures from ehealthme derived from the ADRs submitted by doctors to the FDA and SEDA we find the following:

On Jul, 29, 2015: 772 people reported to have side effects when taking Bromocriptine mesylate. Among them, 27 people (3.50%) have Hallucination.

Trend of Hallucination in Bromocriptine mesylate reports

Time on Bromocriptine mesylate when people have Hallucination  :

  < 1 month 1 - 6 months 6 - 12 months 1 - 2 years 2 - 5 years 5 - 10 years 10+ years
Hallucination 100.00% 0.00% 0.00% 0.00% 0.00% 0.00% 0.00%

Age of people who have Hallucination when taking Bromocriptine mesylate  :

  0-1 2-9 10-19 20-29 30-39 40-49 50-59 60+
Hallucination 0.00% 0.00% 0.00% 3.85% 0.00% 3.85% 0.00% 92.31%

This figure clearly excludes those who are using this drug 'recreationally'.  But we also need to take into account the trade names, so :

On Aug, 11, 2015: 1,795 people reported to have side effects when taking Parlodel. Among them, 77 people (4.29%) have Hallucination.

Trend of Hallucination in Parlodel reports

Time on Parlodel when people have Hallucination  :

  < 1 month 1 - 6 months 6 - 12 months 1 - 2 years 2 - 5 years 5 - 10 years 10+ years
Hallucination 33.33% 33.33% 33.33% 0.00% 0.00% 0.00% 0.00%
 

from Drugs.com
Bromocriptine, alone or in combination with levodopa, may cause hallucinations (visual or auditory). Hallucinations usually resolve with dosage reduction; occasionally, discontinuation of the drug is required. Rarely, after high doses, hallucinations have persisted for several weeks after discontinuation of the drug. Psychiatric side effects have included delusional psychosis, paranoia, depression, anxiety, confusion, "on-off" phenomenon, and nightmares. High doses of bromocriptine may be associated with confusion and mental disturbances (hallucinations). Postmarketing reports suggest that patients treated with antiparkinson medications can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, and other intense urges. Patients may be unable to control these urges while taking the medications used for the treatment of Parkinson's disease and that increase central dopaminergic tone

 

Other side effects

Using the figures from eHealthme again we find that the most common Bromocriptine mesylate side effects, calculated by using ADRs are:

  • Nausea And Vomiting  (53 reports)
  • Nausea  (51 reports)
  • Neuroleptic Malignant Syndrome  (50 reports)
  • Fever (49 reports)
  • Dizziness  (42 reports)
  • Abnormal Behaviour  (37 reports)
  • Headache  (32 reports)
  • Drug Exposure During Pregnancy  (32 reports)
  • Fatigue  (31 reports)
  • Breathing Difficulty  (30 reports)

Other frequent side effects are , orthostatic hypotension,  vomiting through stimulation of the brainstem vomiting centre. Bromocriptine can cause worsening of liver problems. Vasospasms with serious consequences such as myocardial infarction and stroke have been reported.   Pulmonary fibrosis has been reported when bromocriptine was used in high doses for the treatment of Parkinson's disease. 

Most common side effects of Cycloset  by gender  :

Female Male
Somnolence Hypotension
Nausea Dizziness
Hypotension Syncope
Hypoglycaemia Hyperhidrosis
Vomiting Loss Of Consciousness
Dyskinesia Anxiety
Dyspnoea Asthenia
Herpes Zoster Bradycardia
Cerebrovascular Accident Renal Failure Acute
Condition Aggravated Blood Electrolytes Abnormal
 

Death.

 

Using the ehealthme figures and taking a snapshot we find the following. 

We have included the figures under all the tradenames as well

 

 

 

On Aug, 25, 2015: 773 people reported to have side effects when taking Bromocriptine mesylate. Among them, 8 people (1.03%) have Death [source ehealthme].

Trend of Death in Bromocriptine mesylate reports

Time on Bromocriptine mesylate when people have Death  :

  < 1 month 1 - 6 months 6 - 12 months 1 - 2 years 2 - 5 years 5 - 10 years 10+ years
Death 0.00% 0.00% 100.00% 0.00% 0.00% 0.00% 0.00%

Age of people who have Death when taking Bromocriptine mesylate  :

  0-1 2-9 10-19 20-29 30-39 40-49 50-59 60+
Death 0.00% 0.00% 0.00% 0.00% 0.00% 71.43% 14.29% 14.29%

 

On Jul, 30, 2015: 1,795 people reported to have side effects when taking Parlodel. Among them, 17 people (0.95%) have Death.

Trend of Death in Parlodel reports

Time on Parlodel when people have Death  :

  < 1 month 1 - 6 months 6 - 12 months 1 - 2 years 2 - 5 years 5 - 10 years 10+ years
Death 0.00% 100.00% 0.00% 0.00% 0.00% 0.00% 0.00%

 

 

The chemistry of Bromocriptine

Bromocriptine is a potent agonist at dopamine D2 receptors and various serotonin receptors. It also inhibits the release of glutamate, by reversing the glutamate GLT1 transporter.  Bromocriptine agonizes the following monoamine receptors.

  • Dopamine D1 family
    • D1 (Ki=682 nM)
    • D5(Ki=496 nM)
  • Dopamine D2 family
    • D2 (Ki=2.96 nM)
    • D3 (Ki=5.42 nM)
    • D4 (Ki=328 nM)
  • Serotonin 5-HT
    • 5-HT1A (Ki=12.9 nM)
    • 5-HT1B (Ki=355 nM)
    • 5-HT1D (Ki=10.7 nM)
    • 5-HT2A (Ki=107 nM)
    • 5-HT2B (Ki=56.2 nM)
    • 5-HT2C (Ki=741 nM)
    • 5-HT6 (Ki=33 nM)
  •  
    Adrenergic alpha family
    • alpha1A (Ki=4.17 nM)
    • alpha1B (Ki=1.38 nM)
    • alpha1D (Ki=1.12 nM)
    • alpha2A (Ki=11.0 nM)
    • alpha2B (Ki=34.7 nM)
    • alpha2C (Ki=28.2 nM)
  • Adrenergic beta family
    • beta1 (Ki=589 nM)
    • beta2 (Ki=741 nM)

Other properties for serotonin are yet unknown.

How it works

Look at the list - dopamine, serotonin - this is an unbelievable drug to put onto the market. 

Bromocriptine, 2-bromoergocriptine, is a semisynthetic derivative of a natural ergot alkaloid, ergocriptin.  Ergocriptin is a derivative of lysergic acid, which is synthesized by bromination of ergocriptin using N-bromosuccinimide.

The only mechanism that appears to seem plausible as the means by which hallucinations were achieved is poisoning.

But there are also hints that this drug causes serotonin imbalance.

References and further reading

Robert and Shana ParkeHarrison

 

 

The full list of all the Bromocriptine side-effects on the eHealthme website can be seen by following this LINK.

All the photos on this page are by Robert and Shana Parke-Harrison. 

Robert ParkeHarrison (born 1968) is a photographer, best known for his work with wife Shana ParkeHarrison in the area of fine art photography.

My photographs tell stories of loss, human struggle, and personal exploration within landscapes scarred by technology and over-use…. [I] strive to metaphorically and poetically link laborious actions, idiosyncratic rituals and strangely crude machines into tales about our modern experience.

 

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